Skip to main content
SpringerLink
Log in
Book cover

Molecular Basis of Thyroid Cancer pp 237–264Cite as

Molecular Signaling in Thyroid Cancer

  • Chapter

Part of the Cancer Treatment and Research book series (CTAR,volume 122)

Keywords

  • Thyroid Cancer
  • Thyroid Carcinoma
  • Papillary Thyroid Carcinoma
  • Thyroid Tissue
  • Differentiate Thyroid Carcinoma

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Usmani B.A. Genomic instability and metastatic progression. Pathobiology 1993; 61:109–16.

    CAS  PubMed  Google Scholar 

  2. Jimenez E., Pavia J., Morell V., Martin E., Montiel M. Muscarinic receptor subtypes and calcium signaling in Fischer rat thyroid cells. Biochem Pharmacol 2001; 61:337–42.

    CAS  PubMed  Google Scholar 

  3. Danowski J., Kmiec B.L. Histochemical and biochemical studies on the secretory mechanisms of some glands of guinea-pigs treated with histamine. Folia Histochem Cytobiol 2002; 40:213–4.

    CAS  PubMed  Google Scholar 

  4. Kiang J.G., Wang X.D., Ding X.Z., Gist I.D., Smallridge R.C. Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells. Thyroid 1996; 6:475–83.

    CAS  PubMed  Google Scholar 

  5. Karbownik M., Lewinski A. The role of oxidative stress in physiological and pathological processes in the thyroid gland; possible involvement in pineal-thyroid interactions. Neuroendocrinol Lett 2003; 24:293–303.

    CAS  PubMed  Google Scholar 

  6. Suzuki K., Mori A., Lavaroni S., Ulianich L., Miyagi E., Saito J., Nakazato M., Pietrarelli M., Shafran N., Grassadonia A., Kim WB., Consiglio E., Formisano S., Kohn L.D. Thyroglobulin regulates follicular function and heterogeneity by suppressing thyroid-specific gene expression. Biochimie 1999; 81:329–40.

    CrossRef  CAS  PubMed  Google Scholar 

  7. Ulianich L., Suzuki K., Mori A., Nakazato M., Pietrarelli M., Goldsmith P., Pacifico F., Consiglio E., Formisano S., Kohn L.D. Follicular thyroglobulin (TG) suppression of thyroid-restricted genes involves the apical membrane asialoglycoprotein recepto and TG phosphorylation. J Biol Chem 1999; 274:25099–107.

    CrossRef  CAS  PubMed  Google Scholar 

  8. Lewinski A., Pawlikowski M., Cardinali D.P. Thyroid growth-stimulating and growth-inhibiting factors. Biol Signals 1993; 2:313–51.

    CAS  PubMed  Google Scholar 

  9. Kohn L.D., Shimura H., Shimura Y., Hidaka A., Giuliani C., Napolitano G., Ohmori M., Laglia G., Saji M. The thyrotropin receptor. Vitam Horm 1995; 50:287–384.

    CAS  PubMed  Google Scholar 

  10. McGriff N.J., Csako G., Gourgiotis L., Lori C.G., Pucino F., Sarlis N.J. Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med 2002; 34:554–64.

    CAS  PubMed  Google Scholar 

  11. Lalli E., Sassone-Corsi P. Thyroid-stimulating hormone (TSH)-directed induction of the CREM gene in the thyroid gland participates in the long-term desensitization of the TSH receptor. Proc Natl Acad Sci U S A 1995; 92:9633–7.

    CAS  PubMed  Google Scholar 

  12. Metaye T., Menet E., Guilhot J., Kraimps J.L. Expression and activity of G protein-coupled receptor kinases in differentiated thyroid carcinoma. J Clin Endocrinol Metab 2002; 87:3279–86.

    CrossRef  CAS  PubMed  Google Scholar 

  13. Nagayama Y., Tanaka K., Hara T., Namba H., Yamashita S., Taniyama K., Niwa M. Involvement of G protein-coupled receptor kinase-5 in homologous desensitization of the thyrotropin receptor. J Biol Chem 1996; 271:10143–8.

    CAS  PubMed  Google Scholar 

  14. Iacovelli L., Franchetti R., Masini M., De Blasi A. GRK2 and beta-arrestin 1 as negative regulators of thyrotropin receptor-stimulated response. Mol Endocrinol 1996; 10:1138–46.

    CrossRef  CAS  PubMed  Google Scholar 

  15. Cai W.Y., Lukes Y.G., Burch H.B., Djuh Y.Y., Carr F., Wartofsky L., Rhooms P., D’Avis J., Baker J.R., Jr., Burnian K.D. Analysis of human TSH receptor gene and RNA transcripts in patients with thyroid disorders. Autoimmunity 1992; 13:43–50.

    CAS  PubMed  Google Scholar 

  16. Holzapfel H.P., Bergner B., Wonerow P., Paschke R. Expression ot G(alpha)(s) proteins and TSH receptor signalling in hyperfunctioning thyroid nodules with TSH receptor mutations. Eur J Endocrinol 2002; 147:109–16.

    CrossRef  CAS  PubMed  Google Scholar 

  17. Paschke R., Ludgate M. The thyrotropin receptor in thyroid diseases. N Engl J Med 1997; 337:1675–81.

    CrossRef  CAS  PubMed  Google Scholar 

  18. Baloch Z., Livolsi V.A. Detection of an activating mutation of the thyrotropin receptor in a case of an autonomously hyperfunctioning thyroid insular carcinoma. J Clin Endocrinol Metab 1997; 82:3906–8.

    CrossRef  CAS  PubMed  Google Scholar 

  19. Cetani F., Tonacchera M., Pinchera A., Barsacchi R., Basolo F., Miccoli P., Pacini F. Genetic analysis of the TSH receptor gene in differentiated human thyroid carcinomas. J Endocrinol Invest 1999; 22:273–8.

    CAS  PubMed  Google Scholar 

  20. Russo D., Wong M.G., Costante G., Chiefari E., Treseler P.A., Arturi F., Filetti S., Clark O.H. A Val 677 activating mutation of the thyrotropin receptor in a Hurthle cell thyroid carcinoma associated with thyrotoxicosis. Thyroid 1999; 9:13–7.

    CAS  PubMed  Google Scholar 

  21. Matsuo K., Friedman E., Gejman P.V., Fagin J.A. The thyrotropin receptor (TSH-R) is not an oncogene for thyroid tumors: structural studies of the TSH-R and the alpha-subunit of Gs in human thyroid neoplasms. J Clin Endocrinol Metab 1993; 76:1446–51.

    CrossRef  CAS  PubMed  Google Scholar 

  22. Derwahl M., Broecker M., Kraiem Z. Clinical review 101: Thyrotropin may not be the dominant growth factor in benign and malignant thyroid tumors. J Clin Endocrinol Metab 1999; 84:829–34.

    CrossRef  CAS  PubMed  Google Scholar 

  23. Gustavsson B., Hermansson A., Andersson A.C., Grimelius L., Bergh J., Westermark B., Heldin N.E. Decreased growth rate and tumour formation of human anaplastic thyroid carcinoma cells transfected with a human thyrotropin receptor cDNA in NMRI nude mice treated with propylthiouracil. Mol Cell Endocrinol 1996; 121:143–51.

    CrossRef  CAS  PubMed  Google Scholar 

  24. Farfel Z., Bourne H.R., Iiri T. The expanding spectrum of G protein diseases. N Engl J Med 1999; 340:1012–20.

    CrossRef  CAS  PubMed  Google Scholar 

  25. Hepler J.R. Emerging roles for RGS proteins in cell signalling. Trends Pharmacol Sci 1999; 20: 376–82.

    CrossRef  CAS  PubMed  Google Scholar 

  26. Suarez H.G., du Villard J.A., Caillou B., Schlumberger M., Parmentier C., Monier R. gsp mutations in human thyroid tumours. Oncogene 1991; 6:677–9.

    CAS  PubMed  Google Scholar 

  27. Hamacher C., Studer H., Zbaeren J., Schatz H., Derwahl M. Expression of functional stimulatory guanine nucleotide binding protein in nonfunctioning thyroid adenomas is not correlated to adenylate cyclase activity and growth of these tumors. J Clin Endocrinol Metab 1995; 80:1724–32.

    CrossRef  CAS  PubMed  Google Scholar 

  28. Feuillan P.P. McCune-Albright syndrome. Curr Ther Endocrinol Metab 1997; 6:235–9.

    CAS  PubMed  Google Scholar 

  29. Mastorakos G., Mitsiades N.S., Doufas A.G., Koutras D.A. Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report. Thyroid 1997; 7:433–9.

    CAS  PubMed  Google Scholar 

  30. Yang G.C., Yao J.L., Feiner H.D., Roses D.F., Kumar A., Mulder J.E. Lipid-rich follicular carcinoma of the thyroid in a patient with McCune-Albright syndrome. Mod Pathol 1999; 12:969–73.

    CAS  PubMed  Google Scholar 

  31. Collins M.T., Sarlis N.J., Merino M.J., Monroe J., Crawford S.E., Krakoff J.A., Guthrie L.C., Bonat S., Robey P.G., Shenker A. Thyroid carcinoma in the McCune-Albright syndrome: contributory role of activating Gs alpha mutations. J Clin Endocrinol Metab 2003; 88:4413–7.

    CAS  PubMed  Google Scholar 

  32. Michiels F.M., Caillou B., Talbot M., Dessarps-Freichey F., Maunoury M.T. Schlumberger M., Mercken L., Monier R., Feunteun J. Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice. Proc Natl Acad Sci U S A 1994; 91:10488–92.

    CAS  PubMed  Google Scholar 

  33. Zeiger M.A., Saji M., Gusev Y., Westra W.H., Takiyama Y., Dooley W.C., Kohn L.D., Levine M.A. Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice. Endocrinology 1997; 138:3133–40.

    CrossRef  CAS  PubMed  Google Scholar 

  34. Coppee F., Gerard A.C., Denef J.F., Ledent C., Vassart G., Dumont J.E., Parmentier M. Early occurrence of metastatic differentiated thyroid carcinomas in transgenic mice expressing the A2a adenosine receptor gene and the human papillomavirus type 16 E7 oncogene. Oncogene 1996; 13:1471–82.

    CAS  PubMed  Google Scholar 

  35. Allgeier A., Laugwitz K.L., Van Sande J., Schultz G., Dumont J.E. Multiple G-protem coupling of the dog thyrotropin receptor. Mol Cell Endocrinol 1997; 127:81–90.

    CrossRef  CAS  PubMed  Google Scholar 

  36. Ekokoski E., Dugue B., Vainio M., Vainio P.J., Tornquist K. Extracellular ATP-mediated phospholipase A(2) activation in rat thyroid FRTL-5 cells: regulation by a G(i)/G(o) protein, Ca(2+), and mitogen-activated protein kinase. J Cell Physiol 2000; 183:155–62.

    CrossRef  CAS  PubMed  Google Scholar 

  37. Balsinde J., Winstead M.V., Dennis E.A. Phospholipase A(2) regulation of arachidonic acid mobilization. FEBS Lett 2002; 531:2–6.

    CrossRef  CAS  PubMed  Google Scholar 

  38. Smith T.J., Jennings T.A., Sciaky D., Cao H.J. Prostaglandin-endoperoxide H synthase-2 expression in human thyroid epithelium. Evidence for constitutive expression in vivo and in cultured KAT-50 cells. J Biol Chem 1999; 274:15622–32.

    CAS  PubMed  Google Scholar 

  39. Rodrigues S., Nguyen Q.D., Faivre S., Bruyneel E., Thim L., Westley B., May F., Flatau G., Mareel M., Gespach C., Emami S. Activation of cellular invasion by trefoil peptides and src is mediated by cyclooxygenase-and thromboxane A2 receptor-dependent signaling pathways. FASEB J 2001; 15:1517–28.

    CrossRef  CAS  PubMed  Google Scholar 

  40. Ringel M.D., Saji M., Schwindinger W.F., Segev D., Zeiger M.A., Levine M.A. Absence of activating mutations of the genes encoding the alpha-subunits of G11 and Gq in thyroid neoplasia. J Clin Endocrinol Metab 1998; 83:554–9.

    CAS  PubMed  Google Scholar 

  41. Ringel M.D., Hardy E., Bernet V.J., Burch H.B., Schuppert F., Burman K.D., Saji M. Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells. J Clin Endocrinol Metab 2002; 87:2399.

    CrossRef  CAS  PubMed  Google Scholar 

  42. Laugwitz K.L., Allgeier A., Offermanns S., Spicher K., Van Sande J., Dumont J.E., Schultz G. The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families. Proc Natl Acad Sci USA 1996; 93:116–20.

    CrossRef  CAS  PubMed  Google Scholar 

  43. Luttrell L.M., Lefkowitz R.J. The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 2002; 115:455–65.

    CAS  PubMed  Google Scholar 

  44. Voigt C., Holzapfel H., Paschke R. Expression of beta-arrestins in toxic and cold thyroid nodules. FEBS Lett 2000; 486:208–12.

    CrossRef  CAS  PubMed  Google Scholar 

  45. Kimura T., Van Keymeulen A., Golstein J., Fusco A., Dumont J.E., Roger P.P. Regulation of thyroid cell proliferation by TSH and other factors: a critical evaluation of in vitro models. Endocr Rev 2001; 22:631–56.

    CrossRef  CAS  PubMed  Google Scholar 

  46. Dremier S., Coulonval K., Perpete S., Vandeput F., Fortemaison N., Van Keymeulen A., Deleu S., Ledent C., Clement S., Schurmans S., Dumont J.E., Lamy E, Roger P.P., Maenhaut C. The role of cyclic AMP and its effect on protein kinase A in the mitogenic action of thyrotropin on the thyroid cell. Ann N Y Acad Sci 2002; 968:106–21.

    CAS  PubMed  Google Scholar 

  47. Clark O.H. Gerend P.L. Thyrotropin regulation of adenylate cyclase activity in human thyroid neoplasms. Surgery 1985; 97:539–46.

    CAS  PubMed  Google Scholar 

  48. Siperstein A.E., Miller R.A., Landis C., Bourne H., Clark O.H. Increased stimulatory G protein in neoplastic human thyroid tissues. Surgery 1991; 110:949–55.

    CAS  PubMed  Google Scholar 

  49. Kimura H., Yamashita S., Namba H., Usa T., Fujiyama K., Tsuruta M., Yokoyama N., Izumi M., Nagataki S. Impairment of the TSH signal transduction system in human thyroid carcinoma cells. Exp Cell Res 1992; 203:402–6.

    CrossRef  CAS  PubMed  Google Scholar 

  50. Sveshnikov P.G., Grozdova I.D., Nesterova M.V, Severin E.S. Protein kinase A: regulation and receptormediated delivery of antisense oligonucleotides and cytotoxic drugs. Ann NY Acad Sci 2002; 968:158–72.

    CAS  PubMed  Google Scholar 

  51. Esapa C.T., Harris P.E. Mutation analysis of protein kinase A catalytic subunit in thyroid adenomas and pituitary tumours. Eur J Endocrinol 1999; 141:409–12.

    CrossRef  CAS  PubMed  Google Scholar 

  52. Kirschner L.S., Carney J.A., Pack S.D., Taymans S.E., Giatzakis C., Cho Y.S., Cho-Chung Y.S., Stratakis C.A. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000; 26:89–92.

    CAS  PubMed  Google Scholar 

  53. Sandrini F, Matyakhina L., Sarlis N.J., Kirschner L.S., Farmakidis C., Gimm O., Stratakis C.A. Regulatory subunit type I-alpha of protein kinase A (PRKAR1A): a tumor-suppressor gene for sporadic thyroid cancer. Genes Chromosomes Cancer 2002; 35:182–92.

    CrossRef  CAS  PubMed  Google Scholar 

  54. Grange M., Sette C., Cuomo M., Conti M., Lagarde M., Prigent A.F., Nemoz G. The cAMP-specific phosphodiesterase PDE4D3 is regulated by phosphatidic acid binding. Consequences for cAMP signaling pathway and characterization of a phosphatidic acid binding site. J Biol Chem 2000; 275:33379–87.

    CrossRef  CAS  PubMed  Google Scholar 

  55. Sette C., Conti M. Phosphorylation and activation of a cAMP-specific phosphodiesterase by the cAMP-dependent protein kinase. Involvement of serine 54 in the enzyme activation. J Biol Chem 1996; 271:16526–34.

    CAS  PubMed  Google Scholar 

  56. Scott J.D. A-kinase-anchoring proteins and cytoskeletal signalling events. Biochem Soc Trans 2003; 31:87–9.

    CAS  PubMed  Google Scholar 

  57. Ciullo I., Diez-Roux G., Di Domenico M., Migliaccio A., Avvedimento E.V. cAMP signaling selectively influences Ras effectors pathways. Oncogene 2001; 20:1186–92.

    CrossRef  CAS  PubMed  Google Scholar 

  58. Brunetti A., Chiefari E., Filetti S., Russo D. The 3’,5’-cyclic adenosine monophosphate response element binding protein (CREB) is functionally reduced in human toxic thyroid adenomas. Endocrinology 2000; 141:722–30.

    CrossRef  CAS  PubMed  Google Scholar 

  59. Luciani P., Buci L., Conforti B., Tonacchera M., Agretti P., Elisei R., Vivaldi A., Cioppi E, Biliotti G., Manca G., Vitti P., Serio M., Peri A. Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours. Eur J Endocrinol 2003; 148:579–86.

    CrossRef  CAS  PubMed  Google Scholar 

  60. Rosenberg D., Groussin L., Jullian E., Perlemoine K., Bertagna X., Bertherat J. Role of the PKA-regulated transcription factor CREB in development and tumorigenesis of endocrine tissues. Ann N Y Acad Sci 2002; 968:65–74.

    CAS  PubMed  Google Scholar 

  61. Goldman P.S., Tran V.K., Goodman R.H. The multifunctional role of the co-activator CBP in transcriptional regulation. Recent Prog Horm Res 1997; 52:103–20.

    CAS  PubMed  Google Scholar 

  62. Montminy M. Transcriptional regulation by cyclic AMP. Annu Rev Biochem 1997; 66:807–22.

    CrossRef  CAS  PubMed  Google Scholar 

  63. Spaulding S.W., Fucile N.W., Bofinger D.P., Sheflin L.G. Cyclic adenosine 3’,5’-monophosphate-dependent phosphorylation of HMG 14 inhibits its interactions with nucleosomes. Mol Endocrinol 1991; 5:42–50.

    CAS  PubMed  Google Scholar 

  64. Bustin M., Trieschmann L., Postnikov Y.V. The HMG-14/-17 chromosomal protein family: architectural elements that enhance transcription from chromatin templates. Semin Cell Biol 1995; 6:247–55.

    CAS  PubMed  Google Scholar 

  65. Kobayashi K., Shaver J.K., Liang W., Siperstein A.E., Duh Q.Y., Clark O.H. Increased phospholipase C activity in neoplastic thyroid membrane. Thyroid 1993; 3:25–9.

    CAS  PubMed  Google Scholar 

  66. Osborne N.N., Tobin A.B., Ghazi H. Role of inositol trisphosphate as a second messenger in signal transduction processes: an essay. Neurochem Res 1988; 13:177–91.

    CAS  PubMed  Google Scholar 

  67. Mochly-Rosen D., Fagin J.A., Knauf J.A., Nikiforov Y., Liron T, Schechtman D. Spontaneous occurrence of an inhibitor of protein kinase C localization in a thyroid cancer cell line: role in thyroid tumorigenesis. Adv Enzyme Regul 2001; 41:87–97.

    CAS  PubMed  Google Scholar 

  68. Knauf J.A., Ward L.S., Nikiforov Y.E., Nikiforova M., Puxeddu E., Medvedovic M., Liron T., Mochly-Rosen D., Fagin J.A. Isozyme-specific abnormalities of PKC in thyroid cancer: evidence for post-transcriptional changes in PKC-epsilon. J Clin Endocrinol Metab 2002; 87:2150–9.

    CrossRef  CAS  PubMed  Google Scholar 

  69. Heinrich R., Kraiem Z. The protein kinase A pathway inhibits c-jun and c-fos proto-oncogene expression induced by the protein kinase C and tyrosine kinase pathways in cultured human thyroid follicles. J Clin Endocrinol Metab 1997; 82:1839–44.

    CrossRef  CAS  PubMed  Google Scholar 

  70. Francis-Lang H., Zannini M., De Felice M., Berlingieri M.T., Fusco A., Di Lauro R. Multiple mechanisms of interference between transformation and differentiation in thyroid cells. Mol Cell Biol 1992; 12:5793–800.

    CAS  PubMed  Google Scholar 

  71. Ohta K., Pang X.P., Berg L., Hershman J.M. Growth inhibition of new human thyroid carcinoma cell lines by activation of adenylate cyclase through the beta-adrenergic receptor. J Clin Endocrinol Metab 1997; 82:2633–8.

    CrossRef  CAS  PubMed  Google Scholar 

  72. Kosugi S., Mori T., Iwamori M., Nagai Y, Imura H. Alpha 2-and beta-adrenergic receptors and adenosine A1 receptor of FRTL-5 rat thyroid cells in relation to fucosyl GM1-ganglioside. Endocrinology 1989; 124:2707–10.

    CAS  PubMed  Google Scholar 

  73. Shimura H., Endo T., Tsujimoto G., Watanabe K., Hashimoto K., Onaya T. Characterization of alpha 1-adrenergic receptor subtypes linked to iodide efflux in rat FRTL cells. J Endocrinol 1990; 124:433–41.

    CAS  PubMed  Google Scholar 

  74. Ledent C., Denef J.F., Cottecchia S., Lefkowitz R., Dumont J., Vassart G., Parmentier M. Co-stimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells. Endocrinology 1997; 138:369–78.

    CrossRef  CAS  PubMed  Google Scholar 

  75. Fradkin J.E., Hardy W., Wolff J. Adenosine receptor-mediated accumulation of adenosine 3’,5’-monophosphate in guinea pig thyroid tissue. Endocrinology 1982; 110:2018–23.

    CAS  PubMed  Google Scholar 

  76. Sho K., Narita T., Okajima F., Kondo Y. An adenosine receptor agonist-induced modulation of TSH-dependent cell growth in FRTL-5 thyroid cells mediated by inhibitory G protein, Gi. Biochimie 1999;81:341–6.

    CAS  Google Scholar 

  77. Ledent C., Parmentier M., Vassart G., Dumont J.E. Models of thyroid goiter and tumors in transgenic mice. Mol Cell Endocrinol 1994; 100:167–9.

    CrossRef  CAS  PubMed  Google Scholar 

  78. Jackson S., Tseng Y.C., Lahiri S., Burman K.D., Wartofsky L. Receptors for endothelin in cultured human thyroid cells and inhibition by endothelin of thyroglobulin secretion. J Clin Endocrinol Metab 1992; 75:388–92.

    CrossRef  CAS  PubMed  Google Scholar 

  79. Tsushima T., Arai M., Isozaki O., Nozoe Y., Shizume K., Murakami H., Emoto N., Miyakawa M., Demura H. Interaction of endothelin-1 with porcine thyroid cells in culture: a possible autocrine factor regulating iodine metabolism. J Endocrinol 1994; 142:463–70.

    CAS  PubMed  Google Scholar 

  80. Nelson J., Bagnato A., Battistini B., Nisen P. The endothelin axis: emerging role in cancer. Nat Rev-Cancer 2003; 3:110–6.

    CAS  PubMed  Google Scholar 

  81. Donckier J.E., Michel L., Van Beneden R., Delos M., Havaux X. Increased expression of endothelin-1 and its mitogenic receptor ETA in human papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2003; 59:354–60.

    CrossRef  CAS  Google Scholar 

  82. Gualillo O., Lago F., Gomez-Reino J., Casanueva F.F., Dieguez C. Ghrelin, a widespread hormone: insights into molecular and cellular regulation of its expression and mechanism of action. FEBS Lett 2003; 552:105–9.

    CrossRef  CAS  PubMed  Google Scholar 

  83. Gnanapavan S., Kola B., Bustin S.A., Morris D.G., McGee P., Fairclough P., Bhattacharya S., Carpenter R., Grossman A.B., Korbonits M. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 2002; 87:2988.

    CrossRef  CAS  PubMed  Google Scholar 

  84. Volante M., Allia E., Fulcheri E., Cassoni P., Ghigo E., Muccioli G., Papotti M. Ghrelin in fetal thyroid and follicular tumors and cell lines: expression and effects on tumor growth. Am J Pathol 2003; 162:645–54.

    CAS  PubMed  Google Scholar 

  85. Hansen L.H., Abrahamsen N., Nishimura E. Glucagon receptor mRNA distribution in rat tissues. Peptides 1995; 16:1163–6.

    CrossRef  CAS  PubMed  Google Scholar 

  86. Reubi J.C. In vitro evaluation of VIP/PACAP receptors in healthy and diseased human tissues. Clinical implications. Ann N Y Acad Sci 2000; 921:1–25.

    CAS  PubMed  Google Scholar 

  87. Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell 2000; 103:211–25.

    CrossRef  CAS  PubMed  Google Scholar 

  88. Sarlis, Nicholas J., Gourgiotis Loukas. “Molecular Endocrinology.” In Endocrine Surgery, Arthur E. Schwartz, Demetrius Pertsemlides, and Michel Gagner, eds. pp. 1–10, New York, NY, Marcel Dekker, Inc., 2004.

    Google Scholar 

  89. Farid N.R., Shi Y., Zou M. Molecular basis of thyroid cancer. Endocr Rev 1994; 15:202–32.

    CrossRef  CAS  PubMed  Google Scholar 

  90. Bachrach L.K., Nanto-Salonen K., Tapanainen P., Rosenfeld R.G., Gargosky S.E. Insulin-like growth factor binding protein production in human follicular thyroid carcinoma cells. Growth Regul 1995; 5:109–18.

    CAS  PubMed  Google Scholar 

  91. Goffard J.C., Jin L., Mircescu H., Van Hummelen P., Ledent C., Emile Dumont J., Corvilain B. Gene expression profile in thyroid of transgenic mice over-expressing the adenosine receptor 2a. Mol Endocrinol 2003

    Google Scholar 

  92. Vella V., Sciacca L., Pandini G., Mineo R., Squatrito S., Vigneri R., Belfiore A. The IGF system in thyroid cancer: new concepts. Mol Pathol 2001; 54:121–4.

    CAS  PubMed  Google Scholar 

  93. Vella V., Pandini G., Sciacca L., Mineo R., Vigneri R., Pezzino V., Belfiore A. A novel autocrine loop involving IGF-II and the insulin receptor isoform-A stimulates growth of thyroid cancer. J Clin Endocrinol Metab 2002; 87:245–54.

    CrossRef  CAS  PubMed  Google Scholar 

  94. Mitsiades C.S., Poulaki V., Mitsiades N. The role of apoptosis-inducing receptors of the tumor necrosis factor family in thyroid cancer. J Endocrinol 2003; 178:205–16.

    CrossRef  CAS  PubMed  Google Scholar 

  95. Eggo M.C., Hopkins J.M., Franklyn J.A., Johnson G.D., Sanders D.S., Sheppard M.C. Expression of fibroblast growth factors in thyroid cancer. J Clin Endocrinol Metab 1995; 80:1006–11.

    CrossRef  CAS  PubMed  Google Scholar 

  96. Shingu K., Fujimori M., Ito K., Hama Y., Kasuga Y., Kobayashi S., Itoh N., Amano J. Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 in thyroid diseases: difference between neoplasms and hyperplastic lesions. EndocrJ 1998; 45:35–43.

    CAS  Google Scholar 

  97. Viglietto G., Chiappetta G., Martinez-Tello F.J., Fukunaga F.H., Tallini G., Rigopoulou D., Visconti R., Mastro A., Santoro M., Fusco A. RET/PTC oncogene activation is an early event in thyroid carcinogenesis. Oncogene 1995; 11:1207–10.

    CAS  PubMed  Google Scholar 

  98. Duh Q.-Y., Gum E.T., Gerend PL., Raper S.E., Clark O.H. Epidermal growth factor receptors in normal and neoplastic thyroid tissue. Surgery 1985; 98:1000–7.

    CAS  PubMed  Google Scholar 

  99. Gabler B., Aicher T., Heiss P., Senekowitsch-Schmidtke R. Growth inhibition of human papillary thyroid carcinoma cells and multicellular spheroids by anti-EGF-receptor antibody. Anticancer Res 1997; 17:3157–9.

    CAS  PubMed  Google Scholar 

  100. Haugen D.R., Akslen L.A., Varhaug J.E., Lillehaug J.R. Demonstration of a TGF-alpha-EGF-receptor autocrine loop and c-myc protein over-expression in papillary thyroid carcinomas. Int J Cancer 1993; 55: 37–43.

    CAS  PubMed  Google Scholar 

  101. Paez Pereda M., Missale C., Grubler Y., Arzt E., Schaaf L., Stalla G.K. Nerve growth factor and retinoic acid inhibit proliferation and invasion in thyroid tumor cells. Mol Cell Endocrinol 2000; 167:99–106.

    CAS  PubMed  Google Scholar 

  102. Nakada T., Sato H., Inoue F., Mizorogi F., Nagayama K., Tanaka T. The production of colony-stimulating factors by thyroid carcinoma is associated with marked neutrophilia and eosinophilia. Intern Med 1996; 35:815–20.

    CAS  PubMed  Google Scholar 

  103. Aust G., Hofmann A., Laue S., Ode-Hakim S., Scherbaum W.A. Differential regulation of granulocyte-macrophage colony-stimulating factor mRNA and protein expression in human thyrocytes and thyroid-derived fibroblasts by interleukin-1 alpha and tumor necrosis factor-alpha. J Endocrinol 1996; 151:277–85.

    CrossRef  CAS  PubMed  Google Scholar 

  104. Tanaka K., Nagayama Y., Nakano T., Takamura N., Namba H., Fukada S., Kuma K., Yamashita S., Niwa M. Expression profile of receptor-type protein tyrosine kinase genes in the human thyroid. Endocrinology 1998; 139:852–8.

    CAS  PubMed  Google Scholar 

  105. Thompson S.D., Franklyn J.A., Watkinson J.C., Verhaeg J.M., Sheppard M.C., Eggo M.C. Fibroblast growth factors 1 and 2 and fibroblast growth factor receptor 1 are elevated in thyroid hyperplasia. J Clin Endocrinol Metab 1998; 83:1336–41.

    CAS  PubMed  Google Scholar 

  106. Onose H., Emoto N., Sugihara H., Shimizu K., Wakabayashi I. Overexpression of fibroblast growth factor receptor 3 in a human thyroid carcinoma cell line results in overgrowth of the confluent cultures. Eur J Endocrinol 1999; 140:169–73.

    CrossRef  CAS  PubMed  Google Scholar 

  107. Ruco L.P., Stoppacciaro A., Ballarini F., Prat M., Scarpino S. Met protein and hepatocyte growth factor (HGF) in papillary carcinoma of the thyroid: evidence for a pathogenetic role in tumourigenesis. J Pathol 2001; 194:4–8.

    CrossRef  CAS  PubMed  Google Scholar 

  108. Fluge O., Haugen D.R., Akslen L.A., Marstad A., Santoro M., Fusco A., Varhaug J.E., Lillehaug J.R. Expression and alternative splicing of c-ret RNA in papillary thyroid carcinomas. Oncogene 2001; 20:885–92.

    CrossRef  CAS  PubMed  Google Scholar 

  109. Koizumi H., Morita M., Mikami S., Shibayama E., Uchikoshi T. Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas. Pathol Int 1998; 48:93–101.

    CAS  PubMed  Google Scholar 

  110. Meakin S.O., Shooter E.M. The nerve growth factor family of receptors. Trends Neurosci 1992; 15:323–31.

    CrossRef  CAS  PubMed  Google Scholar 

  111. Bunone G., Vigneri R, Mariani L., Buto S., Collini P., Pilotti S., Pierotti M.A., Bongarzone I. Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. Am J Pathol 1999; 155:1967–76.

    CAS  PubMed  Google Scholar 

  112. Shushanov S., Bronstein M., Adelaide J., Jussila L., Tchipysheva T., Jacquemier J., Stavrovskaya A., Birnbaum D., Karamysheva A. VEGFc and VEGFR3 expression in human thyroid pathologies. Int J Cancer 2000; 86:47–52.

    CrossRef  CAS  PubMed  Google Scholar 

  113. Fenton C., Patel A., Dinauer C., Robie D.K., Tuttle R.M., Francis G.L. The expression of vascular endothelial growth factor and the type 1 vascular endothelial growth factor receptor correlate with the size of papillary thyroid carcinoma in children and young adults. Thyroid 2000; 10:349–57.

    CAS  PubMed  Google Scholar 

  114. Trovato M., Villari D., Bartolone L., Spinella S., Simone A., Violi M.A., Trimarchi F., Batolo D., Benvenga S. Expression of the hepatocyte growth factor and c-met in normal thyroid, non-neoplastic, and neoplastic nodules. Thyroid 1998; 8:125–31.

    CAS  PubMed  Google Scholar 

  115. Di Renzo M.F., Olivero M., Ferro S., Prat M., Bongarzone I., Pilotti S., Belfiore A., Costantino A., Vigneri R., Pierotti M.A, et al. Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 1992; 7:2549–53.

    PubMed  Google Scholar 

  116. Belfiore A., Gangemi P., Costantino A., Russo G., Santonocito G.M., Ippolito O., Di Renzo M.E, Comoglio P., Fiumara A., Vigneri R. Negative/low expression of the Met/hepatocyte growth factor receptor identifies papillary thyroid carcinomas with high risk of distant metastases. J Clin Endocrinol Metab 1997; 82:2322–8.

    CrossRef  CAS  PubMed  Google Scholar 

  117. Ramirez R., Hsu D., Patel A., Fenton C., Dinauer C., Tuttle R.M., Francis G.L. Over-expression of hepatocyte growth factor/scatter factor (HGF/SF) and the HGF/SF receptor (cMET) are associated with a high risk of metastasis and recurrence for children and young adults with papillary thyroid carcinoma. Clin Endocrinol (Oxf) 2000; 53:635–44.

    CrossRef  CAS  Google Scholar 

  118. Trovato M., Grosso M., Vitarelli E., Ruggeri R.M., Alesci S., Trimarchi F, Barresi G., Benvenga S. Distinctive expression of STAT3 in papillary thyroid carcinomas and a subset of follicular adenomas. Histol Histopathol 2003; 18:393–9.

    CAS  PubMed  Google Scholar 

  119. Zsebo K.M., Williams D.A., Geissler E.N., Broudy V.C., Martin F.H., Atkins H.L., Hsu R.Y., Birkett N.C., Okino K.H., Murdock D.C., et al. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 1990; 63:213–24.

    CAS  PubMed  Google Scholar 

  120. Tanaka T., Umeki K., Yamamoto I., Kotani T., Sakamoto F., Noguchi S., Ohtaki S. c-Kit proto-oncogene is more likely to lose expression in differentiated thyroid carcinoma than three thyroid-specific genes: thyroid peroxidase, thyroglobulin, and thyroid stimulating hormone receptor. EndocrJ 1995; 42:723–8.

    CAS  Google Scholar 

  121. Natali P.G., Berlingieri M.T., Nicotra M.R., Fusco A., Santoro E., Bigotti A., Vecchio G. Transformation of thyroid epithelium is associated with loss of c-kit receptor. Cancer Res 1995; 55:1787–91.

    CAS  PubMed  Google Scholar 

  122. LeRoith D. Insulin-like growth factor I receptor signaling — overlapping or redundant pathways? Endocrinology 2000; 141:1287–8.

    CrossRef  CAS  PubMed  Google Scholar 

  123. Mercalli E., Ghirzoni S., Arighi E., A Iberti L., Sangregorio R., Radice M.T., Gishizky M.L., Pierotti M.A., Borrello M.G. Key role of Shc signaling in the transforming pathway triggered by Ret/ptc2 oncoprotein. Oncogene 2001; 20:3475–85.

    CrossRef  CAS  PubMed  Google Scholar 

  124. Barbacid M. ras oncogenes: theirrole in neoplasia. Eur J Clin Invest 1990; 20:225–35.

    CAS  PubMed  Google Scholar 

  125. Blalock W.L., Weinstein-Oppenheimer C., Chang F., Hoyle P.E., Wang X.Y., Algate P.A., Franklin R.A., Oberhaus S.M., Steelman L.S., McCubrey J.A. Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs. Leukemia 1999; 13:1109–66.

    CAS  PubMed  Google Scholar 

  126. Monje P., Marinissen M.J., Gutkind J.S. Phosphorylation of the carboxyl-terminal transactivation domain of c-Fos by extracellular signal-regulated kinase mediates the transcriptional activation of AP-1 and cellular transformation induced by platelet-derived growth factor. Mol Cell Biol 2003; 23:7030–43.

    CrossRef  CAS  PubMed  Google Scholar 

  127. Yordy J.S., Muise-Helmericks R.C. Signal transduction and the Ets family of transcription factors. Oncogene 2000; 19:6503–13.

    CrossRef  CAS  PubMed  Google Scholar 

  128. Terrier P., Sheng Z.M., Schlumberger M., Tubiana M., Caillou B., Travagli J.P., Fragu P., Parmentier C., Riou G. Structure and expression of c-myc and c-fos proto-oncogenes in thyroid carcinomas. BrJ Cancer 1988; 57:43–7.

    CAS  Google Scholar 

  129. del Senno L., Gambari R., degli Uberti E., Barbieri R., Bernardi F., Buzzoni D., Marchetti G., Pansini G., Perrotta C., Conconi F. c-myc oncogene alterations in human thyroid carcinomas. Cancer Detect Prev 1987; 10:159–66.

    PubMed  Google Scholar 

  130. Farid N.R. Molecular pathogenesis of thyroid cancer: the significance of oncogenes, tumor suppressor genes, and genomic instability. Exp Clin Endocrinol Diabetes 1996; 104 Suppl 4:1–12.

    CAS  PubMed  Google Scholar 

  131. Nakayama T., Ito M., Ohtsuru A., Naito S., Nakashima M., Sekine I. Expression of the ets-1 proto-oncogene in human thyroid tumor. Mod Pathol 1999; 12:61–8.

    CAS  PubMed  Google Scholar 

  132. de Nigris F., Mega T., Berger N., Barone M.V., Santoro M., Viglietto G., Verde P., Fusco A. Induction of ETS-1 and ETS-2 transcription factors is required for thyroid cell transformation. Cancer Res 2001; 61:2267–75.

    PubMed  Google Scholar 

  133. Dent P., Yacoub A., Contessa J., Caron R., Amorino G., Valerie K., Hagan M.P., Grant S., Schmidt-Ullrich R. Stress and radiation-induced activation of multiple intracellular signaling pathways. Radiat Res 2003; 159:283–300.

    CAS  PubMed  Google Scholar 

  134. Kumar S., Boehm J., Lee J.C. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov 2003; 2:717–26.

    CrossRef  CAS  PubMed  Google Scholar 

  135. Wang X.S., Diener K., Manthey C.L., Wang S., Rosenzweig B., Bray J., Delaney J., Cole C.N., Chan-Hui P.Y., Mantlo N., Lichenstein H.S., Zukowski M., Yao Z. Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase. J Biol Chem 1997; 272:23668–74.

    CAS  PubMed  Google Scholar 

  136. Pomerance M., Abdullah H.B., Kamerji S., Correze C., Blondeau J.P. Thyroid-stimulating hormone and cyclic AMP activate p38 mitogen-activated protein kinase cascade. Involvement of protein kinase A, rac1, and reactive oxygen species. J Biol Chem 2000; 275:40539–46.

    CrossRef  CAS  PubMed  Google Scholar 

  137. Kimura E.T., Nikiforova M.N., Zhu Z., Knauf J.A., Nikiforov Y.E., Fagin J.A. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 2003; 63:1454–7.

    CAS  PubMed  Google Scholar 

  138. Nikiforova M.N., Kimura E.T., Gandhi M., Biddinger P.W., Knauf J.A., Basolo F., Zhu Z., Giannini R., Salvatore G., Fusco A., Santoro M., Fagin J.A., Nikiforov Y.E. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 2003; 88:5399–404.

    CAS  PubMed  Google Scholar 

  139. Cantley L.C. Growth factors bind receptor tyrosine kinases to stimulate cell survival, cell division, cell growth, and cytoskeletal rearrangement. Sci STKE 2003; 2003:tr8.

    Google Scholar 

  140. Cantley L.C. The phosphoinositide 3-kinase pathway. Science 2002; 296:1655–7.

    CrossRef  CAS  PubMed  Google Scholar 

  141. Li J., Yen C., Liaw D., Podsypanina K., Bose S., Wang S.I., Puc J., Miliaresis C., Rodgers L., McCombie R., Bigner S.H., Giovanella B.C., Ittmann M., Tycko B., Hibshoosh H., Wigler M.H., Parsons R. PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 1997; 275:1943–7.

    CrossRef  CAS  PubMed  Google Scholar 

  142. Longy M., Lacombe D. Cowden disease. Report of a family and review. Ann Genet 1996; 39:35–42.

    CAS  PubMed  Google Scholar 

  143. Cantley L.C., Neel B.G. New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci USA 1999; 96: 4240–5.

    CrossRef  CAS  PubMed  Google Scholar 

  144. Halachmi N., Halachmi S., Evron E., Cairns P., Okami K., Saji M., Westra W.H., Zeiger M.A., Jen J., Sidransky D. Somatic mutations of the PTEN tumor suppressor gene in sporadic follicular thyroid tumors. Genes Chromosomes Cancer 1998; 23:239–43.

    CrossRef  CAS  PubMed  Google Scholar 

  145. Ringel M.D., Hayre N., Saito J., Saunier B., Schuppert F., Burch H., Bernet V., Burman K.D., Kohn L.D., Saji M. Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res 2001; 61:6105–11.

    CAS  PubMed  Google Scholar 

  146. De Vita G., Berlingieri M.T., Visconti R., Castellone M.D., Viglietto G., Baldassarre G., Zannini M., Bellacosa A., Tsichlis P.N., Fusco A., Santoro M. Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects. Cancer Res 2000; 60:3916–20.

    PubMed  Google Scholar 

  147. Lemonnier L.A., Dillehay D.L., Vespremi M.J., Abrams J., Brody E., Schmelz E.M. Sphingomyelin in the suppression of colon tumors: prevention versus intervention. Arch Biochem Biophys 2003; 419:129–38.

    CrossRef  CAS  PubMed  Google Scholar 

  148. Sautin Y., Takamura N., Shklyaev S., Nagayama Y., Ohtsuru A., Namba H., Yamashita S. Ceramide-induced apoptosis of human thyroid cancer cells resistant to apoptosis by irradiation. Thyroid 2000; 10:733–40.

    CAS  PubMed  Google Scholar 

  149. Schulte K.M., Beyer A., Kohrer K., Oberhauser S., Roher H.D. Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer. Int J Cancer 2001; 92:249–56.

    CrossRef  CAS  PubMed  Google Scholar 

  150. Alberti L., Carniti C., Miranda C., Roccato E., Pierotti M.A. RET and NTRK1 proto-oncogenes in human diseases. J Cell Physiol 2003; 195:168–86.

    CrossRef  CAS  PubMed  Google Scholar 

  151. Sarlis N.J. Expression patterns of cellular growth-controlling genes in non-medullary thyroid cancer: basic aspects. Rev Endocr Metab Disord 2000; 1:183–96.

    CrossRef  CAS  PubMed  Google Scholar 

  152. Borrello M.G., Pelicci G., Arighi E., De Filippis L., Greco A., Bongarzone I., Rizzetti M., Pelicci P.G., Pierotti M.A. The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins. Oncogene 1994; 9:1661–8.

    CAS  PubMed  Google Scholar 

  153. Asakawa H., Kobayashi T. The secretion of cytokines and granulocyte colony stimulating factor by anaplastic and poorly differentiated thyroid carcinoma cell lines. Anticancer Res 1999; 19:761–4.

    CAS  PubMed  Google Scholar 

  154. Scarpino S., Stoppacciaro A., Ballerini F., Marchesi M., Prat M., Stella M.C., Sozzani S., Allavena P., Mantovani A., Ruco L.P. Papillary carcinoma of the thyroid: hepatocyte growth factor (HGF) stimulates tumor cells to release chemokines active in recruiting dendritic cells. Am J Pathol 2000; 156: 831–7.

    CAS  PubMed  Google Scholar 

  155. Basolo F., Fiore L., Pollina L., Fontanini G., Conaldi P.G., Toniolo A. Reduced expression of interleukin 6 in undifferentiated thyroid carcinoma: in vitro and in vivo studies. Clin Cancer Res 1998; 4:381–7.

    CAS  PubMed  Google Scholar 

  156. Fiore L., Pollina L.E., Fontanini G., Casalone R., Berlingieri M.T., Giannini R., Pacini F., Miccoli P., Toniolo A., Fusco A., Basolo F. Cytokine production by a new undifferentiated human thyroid carcinoma cell line, FB-1. J Clin Endocrinol Metab 1997; 82:4094–100.

    CrossRef  CAS  PubMed  Google Scholar 

  157. Ruggeri R.M., Villari D., Simone A., Scarfi R., Attard M., Orlandi F., Barresi G., Trimarchi F., Trovato M., Benvenga S. Co-expression of interleukin-6 (IL-6) and interleukin-6 receptor (IL-6R) in thyroid nodules is associated with co-expression of CD30 ligand/CD30 receptor. J Endocrinol Invest 2002; 25:959–66.

    CAS  PubMed  Google Scholar 

  158. Chang J.W., Yeh K.Y., Shen Y.C., Hsieh J.J., Chuang C.K., Liao S.K., Tsai L.H., Wang C.H. Production of multiple cytokines and induction of cachexia in athymic nude mice by a new anaplastic thyroid carcinoma cell line. J Endocrinol 2003; 179:387–94.

    CrossRef  CAS  PubMed  Google Scholar 

  159. Kurebayashi J., Tanaka K., Otsuki T., Moriya T., Kunisue H.,U no M., Sonoo H. All-trans-retinoic acid modulates expression levels of thyroglobulin and cytokines in a new human poorly differentiated papillary thyroid carcinoma cell line, KTC-1. J Clin Endocrinol Metab 2000; 85:2889–96.

    CrossRef  CAS  PubMed  Google Scholar 

  160. Weetman A.P., Bright-Thomas R., Freeman M. Regulation of interleukin-6 release by human thyrocytes. J Endocrinol 1990; 127:357–61.

    CAS  PubMed  Google Scholar 

  161. Zeki K., Morimoto I., Arao T., Eto S., Yamashita U. Interleukin-1alpha regulates G1 cell cycle progression and arrest in thyroid carcinoma cell lines NIM1 and NPA. J Endocrinol 1999; 160:67–73.

    CrossRef  CAS  PubMed  Google Scholar 

  162. Matsumura M., Banba N., Motohashi S., Hattori Y. Interleukin-6 and transforming growth factor-beta regulate the expression of monocyte chemoattractant protein-1 and colony-stimulating factors in human thyroid follicular cells. Life Sci 1999; 65:PL129–35.

    CrossRef  CAS  PubMed  Google Scholar 

  163. Stassi G., Todaro M., Zerilli M., Ricci-Vitiani L., Di Liberto D., Patti M., Florena A., Di Gaudio F., Di Gesu G., De Maria R. Thyroid cancer resistance to chemotherapeutic drugs via autocrine production of interleukin-4 and interleukin-10. Cancer Res 2003; 63:6784–90.

    CAS  PubMed  Google Scholar 

  164. Yeh T.C., Pellegrini S. The Janus kinase family of protein tyrosine kinases and their role in signaling. Cell Mol Life Sci 1999; 55:1523–34.

    CAS  PubMed  Google Scholar 

  165. Hirano T. Interleukin 6 and its receptor: ten years later. Int Rev Immunol 1998; 16:249–84.

    CAS  PubMed  Google Scholar 

  166. Ogata A., Chauhan D., Teoh G., Treon S.P., Urashima M., Schlossman R.L., Anderson K.C. IL-6 triggers cell growth via the Ras-dependent mitogen-activated protein kinase cascade. J Immunol 1997; 159:2212–21.

    CAS  PubMed  Google Scholar 

  167. Wang S., El-Deiry W.S. TRAIL and apoptosis induction by TNF-family death receptors. Oncogene 2003; 22; 8628–33.

    CAS  PubMed  Google Scholar 

  168. Yu J., Zhang L. Apoptosis in human cancer cells. Curr Opin Oncol 2004; 16: 19–24.

    PubMed  Google Scholar 

  169. Griffith T.S., Chin W.A., Jackson G.C., Lynch D.H., Kubin M.Z. Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J Immunol 1998; 161:2833–40.

    CAS  PubMed  Google Scholar 

  170. Sarlis N.J., Gourgiotis L. Molecular elements of apoptosis-regulating pathways in follicular thyroid cells: mining for novel therapeutic targets in the treatment of thyroid carcinoma. Curr Drug Targets Immune Endocr Metabol Disord 2004 (in press).

    Google Scholar 

  171. Yamakawa M., Yamada K., Orui H., Tsuge T., Ogata T., Dobashi M., Imai Y. Immunohistochemical analysis of dendritic/Langerhans cells in thyroid carcinomas. Anal Cell Pathol 1995; 8:331–43.

    CAS  PubMed  Google Scholar 

  172. Aust G., Heuer M., Laue S., Lehmann I., Hofmann A., Heldin N.E., Scherbaum W.A. Expression of tumour necrosis factor-alpha (TNF-alpha) mRNA and protein in pathological thyroid tissue and carcinoma cell lines. Clin Exp Immunol 1996; 105:148–54.

    CrossRef  CAS  PubMed  Google Scholar 

  173. Pang X.P., Hershman J.M., Chung M., Pekary A.E. Characterization of tumor necrosis factor-alpha receptors in human and rat thyroid cells and regulation of the receptors by thyrotropin. Endocrinology 1989; 125:1783–8.

    CAS  PubMed  Google Scholar 

  174. Wajant H., Pfizenmaier K., Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003; 10:45–65.

    CrossRef  CAS  PubMed  Google Scholar 

  175. Shaulian E., Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol 2002; 4:E131–6.

    CrossRef  CAS  PubMed  Google Scholar 

  176. Chang L., Karin M. Mammalian MAP kinase signalling cascades. Nature 2001; 410:37–40.

    CAS  PubMed  Google Scholar 

  177. Thatte U., Dahanukar S. Apoptosis: clinical relevance and pharmacological manipulation. Drugs 1997; 54:511–32.

    CAS  PubMed  Google Scholar 

  178. Fisher D.E. Pathways of apoptosis and the modulation of cell death in cancer. Hematol Oncol Clin North Am 2001; 15:931–56.

    CrossRef  CAS  PubMed  Google Scholar 

  179. Giordano C., Stassi G., De Maria R., Todaro M., Richiusa P., Papoff G., Ruberti G., Bagnasco M., Testi R., Galluzzo A. Potential involvement of Fas and its ligand in the pathogenesis of Hashimoto’s thyroiditis. Science 1997; 275:960–3.

    CAS  PubMed  Google Scholar 

  180. Baker J.R., Jr. Dying (apoptosing?) for a consensus on the Fas death pathway in the thyroid. J Clin Endocrinol Metab 1999; 84:2593–5.

    CrossRef  CAS  PubMed  Google Scholar 

  181. Mitsiades N., Poulaki V., Tseleni-Balafouta S., Koutras D.A., Stamenkovic I. Thyroid carcinoma cells are resistant to FAS-mediated apoptosis but sensitive tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res 2000; 60:4122–9.

    CAS  PubMed  Google Scholar 

  182. Borgerson K.L., Bretz J.D., Baker J.R., Jr. The role of Fas-mediated apoptosis in thyroid autoimmune disease. Autoimmunity 1999; 30:251–64.

    CAS  PubMed  Google Scholar 

  183. Lin J.D. The role of apoptosis in autoimmune thyroid disorders and thyroid cancer. Br Med J 2001; 322:1525–7.

    CAS  Google Scholar 

  184. Ogasawara J., Watanabe-Fukunaga R., Adachi M., Matsuzawa A., Kasugai T., Kitamura Y., Itoh N., Suda T., Nagata S. Lethal effect of the anti-Fas antibody in mice. Nature 1993; 364:806–9.

    CrossRef  CAS  PubMed  Google Scholar 

  185. Tourneur L., Mistou S., Michiels F.M., Devauchelle V., Renia L., Feunteun J., Chiocchia G. Loss of FADD protein expression results in a biased Fas-signaling pathway and correlates with the development of tumoral status in thyroid follicular cells. Oncogene 2003; 22:2795–804.

    CrossRef  CAS  PubMed  Google Scholar 

  186. Mitsiades N., Poulaki V., Mitsiades C.S., Koutras D.A., Chrousos G.P. Apoptosis induced by FasL and TRAIL/Apo2L in the pathogenesis of thyroid diseases. Trends Endocrinol Metab 2001; 12:384–90.

    CAS  PubMed  Google Scholar 

  187. Manetto V., Lorenzini R., Cordon-Cardo C., Krajewski S., Rosai J., Rced J.C., Eusebi V. Bcl-2 and Bax expression in thyroid tumours. An immunohistochemical and western blot analysis. Virchows Arch 1997; 430:125–30.

    CrossRef  CAS  PubMed  Google Scholar 

  188. Pestereli H.E., Ogus M., Oren N., Karpuzoglu G., Karpuzoglu T. Bcl-2 and p53 expression in insular and in well-differentiated thyroid carcinomas with an insular pattern. Endocr Pathol 2001; 12:301–5.

    CAS  PubMed  Google Scholar 

  189. Ito Y., Yoshida H., Nakano K., Takamura Y., Miya A., Kobayashi K., Yokozawa T., Matsuzuka F., Matsuura N., Kakudo K., Kuma K., Miyauchi A. Bag-1 expression in thyroid neoplasm: its correlation with Bcl-2 expression and carcinoma dedifferentiation. Anticancer Res 2003; 23: 569–76.

    CAS  PubMed  Google Scholar 

  190. Shi Y., Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003; 113:685–700.

    CrossRef  CAS  PubMed  Google Scholar 

  191. Franzen A., Piek E., Westermark B., ten Dijke P., Heldin N.E. Expression of transforming growth factor-beta1, activin A, and their receptors in thyroid follicle cells: negative regulation of thyrocyte growth and function. Endocrinology 1999; 140: 4300–10.

    CrossRef  CAS  PubMed  Google Scholar 

  192. West J., Munoz-Antonia T., Johnson J.G., Klotch D., Muro-Cacho C.A. Transforming growth factor-beta type II receptors and smad proteins in follicular thyroid tumors. Laryngoscope 2000; 110: 1323–7.

    CAS  PubMed  Google Scholar 

  193. Jasani B., Wyllie F.S., Wright P.A., Lemoine N.R., Williams E.D., Wynford-Thomas D. Immunocy-tochemically detectable TGF-beta associated with malignancy in thyroid epithelial neoplasia. Growth Factors 1990;2: 149–55.

    CAS  PubMed  Google Scholar 

  194. Kimura E.T., Kopp P., Zbaeren J., Asmis L.M., Ruchti C., Maciel R.M., Studer H. Expression of transforming growth factor beta1, beta2, and beta3 in multmodular goiters and differentiated thyroid carcinomas: a comparative study. Thyroid 1999; 9: 119–25.

    CAS  PubMed  Google Scholar 

  195. Schulte K.M., Jonas C., Krebs R., Roher H.D. Activin A and activin receptors in thyroid cancer. Thyroid 2001; 11: 3–14.

    CrossRef  CAS  PubMed  Google Scholar 

  196. Hatakeyama S., Gao Y.H., Ohara-Nemoto Y., Kataoka H., Satoh M. Expression of bone morphogenetic proteins of human neoplastic epithelial cells. Biochem Mol Biol Int. 1997; 42: 497–505.

    CAS  PubMed  Google Scholar 

  197. Attisano L., Wrana J.L. Signal transduction by the TGF-beta superfamily. Science 2002; 296: 1646–7.

    CrossRef  CAS  PubMed  Google Scholar 

  198. Miyazawa K., Shinozaki M., Hara T., Furuya T., Miyazono K. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells 2002; 7: 1191–204.

    CrossRef  CAS  PubMed  Google Scholar 

  199. Ellenrieder V., Buck A., Gress T.M. TGFbeta-regulated transcriptional mechanisms in cancer. Int J Gastrointest Cancer 2002; 31: 61–9.

    CAS  PubMed  Google Scholar 

  200. Lazzereschi D., Ranieri A., Mincione G., Taccogna S., Nardi F., Colletta G. Human malignant thyroid tumors displayed reduced levels of transforming growth factor beta receptor type II messenger RNA and protein. Cancer Res 1997; 57: 2071–6.

    CAS  PubMed  Google Scholar 

  201. Blaydes J.P., Wynford-Thomas D. Loss of responsiveness to transforming growth factor beta (TGFbeta) is tightly linked to tumorigenicity in a model of thyroid tumour progression. Int J Cancer 1996; 65: 525–30.

    CrossRef  CAS  PubMed  Google Scholar 

  202. Heldin N.E., Bergstrom D., Hermansson A., Bergenstrahle A., Nakao A., Westermark B., ten Dijke P. Lack of responsiveness to TGF-beta1 in a thyroid carcinoma cell line with functional type I and type II TGF-beta receptors and Smad proteins, suggests a novel mechanism tor TGF-beta insensitivity in carcinoma cells. Mol Cell Endocrinol 1999; 153: 79–90.

    CrossRef  CAS  PubMed  Google Scholar 

  203. Cerutti J.M., Ebina K.N., Matsuo S.E., Martins L., Maciel R.M., Kimura E.T. Expression of Smad4 and Smad7 in human thyroid follicular carcinoma cell lines. J Endocrinol Invest 2003; 26: 516–21.

    CAS  PubMed  Google Scholar 

  204. Bravo S.B., Pampin S., Cameselle-Teijeiro J., Carneiro C., Dominguez F., Barreiro F., Alvarez C.V. TGF-beta-induced apoptosis in human thyrocytes is mediated by p27kipl reduction and is overridden in neoplastic thyrocytes by NF-kappaB activation. Oncogene 2003; 22: 7819–30.

    CrossRef  CAS  PubMed  Google Scholar 

  205. Blaydes J.P., Schlumberger M., Wynford-Thomas D., Wyllie F.S. Interaction between p53 and TGF beta 1 in control of epithelial cell proliferation. Oncogene 1995; 10: 307–17.

    CAS  PubMed  Google Scholar 

  206. Mincione G., Esposito D.L., Di Marcantonio M.C., Piccirelli A., Cama A., Colletta G. TGF-beta 1 modulation of IGF-I signaling pathway in rat thyroid epithelial cells. Exp Cell Res 2003; 287: 411–23.

    CrossRef  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrine Neoplasia & Hormonal Disorders, The University of Texas - M. D. Anderson Cancer Center, Houston, Texas, 77082, USA

    Nicholas J. Sarlis

  2. Sezione di Endocrinologia, Dipartimento Clinico Sperimentale di Medicina e Farmacologia & Programma di Endocrinologia Molecolare Clinica, University of Messina, Messina, I-98151, Italy

    Salvatore Benvenga

Authors
  1. Nicholas J. Sarlis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Salvatore Benvenga
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Osancor Biotech, Inc., Watford, WD17 3BY, Herts, UK

    Nadir R. Farid

Rights and permissions

Reprints and Permissions

Copyright information

© 2005 Springer Science + Business Media, Inc.

About this chapter

Cite this chapter

Sarlis, N.J., Benvenga, S. (2005). Molecular Signaling in Thyroid Cancer. In: Farid, N.R. (eds) Molecular Basis of Thyroid Cancer. Cancer Treatment and Research, vol 122. Springer, Boston, MA. https://doi.org/10.1007/1-4020-8107-3_14

Download citation

  • DOI: https://doi.org/10.1007/1-4020-8107-3_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-8106-4

  • Online ISBN: 978-1-4020-8107-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

search

Navigation