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The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines

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Abstract

The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3′,5′-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3′,5′-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3′,5′-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

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References

  1. J.A. Sipos, M.H. Shah, Thyroid cancer: emerging role for targeted therapies. Ther. Adv. Med. Oncol. 2, 3–16 (2010). doi:10.1177/1758834009352667

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. G. Vitale, M. Caraglia, A. Ciccarelli, G. Lupoli, A. Abbruzzese, P. Tagliaferri, G. Lupoli, Current approaches and perspectives in the therapy of medullary thyroid carcinoma. Cancer 91, 1797–1808 (2001). doi:10.1002/1097-0142(20010501)91:9

    Article  PubMed  CAS  Google Scholar 

  3. G.I. Manfredi, A. Dicitore, G. Gaudenzi, M. Caraglia, L. Persani, G. Vitale, PI3K/Akt/mTOR signaling in medullary thyroid cancer: a promising molecular target for cancer therapy. Endocrine (2014). doi:10.1007/s12020-014-0380-1

    PubMed  Google Scholar 

  4. G. Vitale, G. Lupoli, R. Guarrasi, A. Colao, A. Dicitore, G. Gaudenzi, G. Misso, M. Castellano, R. Addeo, G. Facchini et al., Interleukin-2 and lanreotide in the treatment of medullary thyroid cancer: in vitro and in vivo studies. J. Clin. Endocrinol. Metab. 98, 1567–1574 (2013). doi:10.1210/jc.2013-1443

    Article  CAS  Google Scholar 

  5. A. Faggiano, V. Ramundo, A. Dicitore, S. Castiglioni, M.O. Borghi, R. Severino, P. Ferolla, L. Crinò, A. Abbruzzese, P. Sperlongano et al., Everolimus is an active agent in medullary thyroid cancer: a clinical and in vitro study. J. Clin. Endocrinol. Metab. 16, 1563–1572 (2012). doi:10.1111/j.1582-4934.2011.01438.x

    CAS  Google Scholar 

  6. O. Gimm, H. Dralle, in Sporadic and hereditary medullary carcinoma, ed. by R.G. Holzheimer, J.A. Mannick. Surgical treatment: evidence-based and problem-oriented (Zuckschwerdt, Munich, 2001)

    Google Scholar 

  7. T. Fukuda, K. Kiuchi, M. Takahashi, Novel mechanism of regulation of rac activity and lamellipodia formation by RET tyrosine kinase. J. Biol. Chem. 277, 19114–19121 (2002). doi:10.1074/jbc.M200643200

    Article  PubMed  CAS  Google Scholar 

  8. N. Asai, T. Fukuda, Z. Wu, A. Enomoto, V. Pachnis, M. Takahashi, F. Costantini, Targeted mutation of serine 697 in the RET tyrosine kinase causes migration defect of enteric neural crest cells. Development 133, 4507–4516 (2006). doi:10.1242/dev.02616

    Article  PubMed  CAS  Google Scholar 

  9. S. Naviglio, D. Di Gesto, M. Romano, A. Sorrentino, F. Illiano, L. Sorvillo, A. Abbruzzese, M. Marra, M. Caraglia, E. Chiosi et al., Leptin enhances growth inhibition by cAMP elevating agents through apoptosis of MDA-MB-231 breast cancer cells. Cancer Biol. Ther. 8, 1183–1190 (2009). doi:10.4161/cbt.8.12.8562

    Article  PubMed  CAS  Google Scholar 

  10. G. Vitale, A. Dicitore, D. Mari, F. Cavagnini, A new therapeutic strategy against cancer: cAMP elevating drugs and leptin. Cancer Biol. Ther. 8, 1191–1193 (2009). doi:10.4161/cbt.8.12.8937

    Article  PubMed  CAS  Google Scholar 

  11. D. Øgreid, S.O. Døskeland, Cyclic nucleotides modulate the release of [3H] adenosine cyclic 3′,5′-phosphate bound to the regulatory moiety of protein kinase I by the catalytic subunit of the kinase. Biochemistry 29, 1686–1696 (1983)

    Article  Google Scholar 

  12. Y.S. Cho-Chung, S. Pepe, T. Clair, A. Budillon, M. Nesterova, 1995 cAMP-dependent protein kinase: role in normal and malignant growth. Crit. Rev. Oncol. Hematol. 21, 33–61 (1995)

    Article  PubMed  CAS  Google Scholar 

  13. X. Cheng, Z. Ji, T. Tsalkova, F. Mei, Epac and PKA: a tale of two intracellular cAMP receptors. Acta Biochim. Biophys. Sin. 40, 651–662 (2008). doi:10.1111/j.1745-7270.2008.00438.x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. M. Unoki, Current and potential anticancer drugs targeting members of the UHRF1 complex including epigenetic modifiers. Recent Pat. Anticancer Drug Discov. 6, 116–130 (2011). doi:10.2174/157489211793980024

    Article  PubMed  CAS  Google Scholar 

  15. Y.H. Ahn, J.M. Jung, S.H. Hong, 8-chloro-cAMP-induced growth inhibition and apoptosis is mediated by p38 mitogen-activated protein kinase activation in HL60 cells. Cancer Res. 65, 4896–4901 (2005). doi:10.1158/0008-5472.CAN-04-3122

    Article  PubMed  CAS  Google Scholar 

  16. S. Lucchi, D. Calebiro, T. De Filippis, E.S. Grassi, M.O. Borghi, L. Persani, 8-Chloro-cyclic AMP and protein kinase A I-selective cyclic AMP analogs inhibit cancer cell growth through different mechanisms. PLoS One 6, 20785 (2011). doi:10.1371/journal.pone.0020785

    Article  CAS  Google Scholar 

  17. P. Tagliaferri, D. Katsaros, T. Clair, S. Ally, G. Tortora, L. Neckers, B. Rubalcava, Z. Parandoosh, Y.A. Chang, G.R. Revankar et al., Synergistic inhibition of growth of breast and colon human cancer cell lines by site-selective cyclic AMP analogues. Cancer Res. 15, 1642–1650 (1988)

    Google Scholar 

  18. S. Ally, T. Clair, D. Katsaros, G. Tortora, H. Yokozaki, R.A. Finch, T.L. Avery, Y.S. Cho-Chung, Inhibition of growth and modulation of gene expression in human lung carcinoma in athymic mice by site-selective 8-Cl-cyclic adenosine monophosphate. Cancer Res. 49, 5650–5655 (1989)

    PubMed  CAS  Google Scholar 

  19. G. Tortora, F. Ciardiello, S. Ally, T. Clair, D.S. Salomon, Y.S. Cho-Chung, Site-selective 8-chloroadenosine 3′,5′-cyclic monophosphate inhibits transformation and transforming growth factor alpha production in Ki-ras-transformed rat fibroblasts. FEBS Lett. 242, 363–367 (1989). doi:10.1016/0014-5793(89)80502-2

    Article  PubMed  CAS  Google Scholar 

  20. F. Ciardiello, G. Tortora, S. Pepe, C. Bianco, G. Baldassarre, A. Ruggiero, C. Bianco, M.P. Selvam, A.R. Bianco, Reduction of RI alpha subunit of cAMP-dependent protein kinase expression induces growth inhibition of human mammary epithelial cells transformed by TGF-alpha, c-Ha-ras, and c-erbB-2 genes. Ann. NY Acad. Sci. 698, 102–107 (1993). doi:10.1111/j.1749-6632.1993.tb17194.x

    Article  PubMed  CAS  Google Scholar 

  21. C. Rohlff, T. Clair, Y.S. Cho-Chung, 8-Cl-cAMP induces truncation and down-regulation of the RI alpha subunit and up-regulation of the RII beta subunit of cAMP-dependent protein kinase leading to type II holoenzyme-dependent growth inhibition and differentiation of HL-60 leukemia cells. J. Biol. Chem. 268, 5774–5782 (1993)

    PubMed  CAS  Google Scholar 

  22. C. Bianco, G. Tortora, G. Baldassarre, R. Caputo, G. Fontanini, S. Chinè, A.R. Bianco, F. Ciardiello, 8-Chloro-cyclic AMP inhibits autocrine and angiogenic growth factor production in human colorectal and breast cancer. Clin. Cancer Res. 3, 439–448 (1997)

    PubMed  CAS  Google Scholar 

  23. D. Ogreid, R. Ekanger, R.H. Suva, J.P. Miller, P. Sturm, J.D. Corbin, S.O. Døskeland, Activation of protein kinase isozymes by cyclic nucleotide analogs used singly or in combination. Principles for optimizing the isozyme specificity of analog combinations. Eur. J. Biochem. 150, 219–227 (1985). doi:10.1111/j.1432-1033.1985.tb09010.x

    Article  PubMed  CAS  Google Scholar 

  24. C.M. Braun, S.K. Huang, A. Kagey-Sobotka, L.M. Lichtenstein, D.M. Essayan, Co-regulation of antigen-specific T lymphocyte responses by type I and type II cyclic AMP-dependent protein kinases (cAK). Biochem. Pharmacol. 56, 871–879 (1998). doi:10.1016/S0006-2952(98)00238-X

    Article  PubMed  CAS  Google Scholar 

  25. D. Calebiro, T. de Filippis, S. Lucchi, C. Covino, S. Panigone, P. Beck-Peccoz, D. Dunlap, L. Persani, Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. Hum. Mol. Genet. 15, 2991–3002 (2005). doi:10.1093/hmg/ddi329

    Article  CAS  Google Scholar 

  26. G. Mantovani, A.G. Lania, S. Bondioni, E. Peverelli, C. Pedroni, S. Ferrero, C. Pellegrini, L. Vicentini, G. Arnaldi, S. Bosari et al., Different expression of protein kinase A (PKA) regulatory subunits in cortisol-secreting adrenocortical tumors: relationship with cell proliferation. Exp. Cell Res. 314, 123–130 (2008). doi:10.1016/j.yexcr.2007.08.024

    Article  PubMed  CAS  Google Scholar 

  27. E. Abemayor, N. Sidell, G. Juillard, Human medullary thyroid carcinoma. Initial characterization and in vitro differentiation of two new cell lines. Arch. Otolaryngol. Head Neck Surg. 115, 478–483 (1989). doi:10.1001/archotol.1989.01860280076020

    Article  PubMed  CAS  Google Scholar 

  28. T. Nakagawa, B.D. Nelkin, S.B. Baylin, A. de Bustros, Transcriptional and posttranscriptional modulation of calcitonin gene expression by sodium n-butyrate in cultured human medullary thyroid carcinoma. Cancer Res. 48, 2096–2100 (1988)

    PubMed  CAS  Google Scholar 

  29. G. Vitale, S. Zappavigna, M. Marra, A. Dicitore, S. Meschini, M. Condello, G. Arancia, S. Castiglioni, P. Maroni, P. Bendinelli et al., The PPAR-γ agonist troglitazone antagonizes survival pathways induced by STAT-3 in recombinant interferon-β treated pancreatic cancer cells. Biotech. Adv. 30, 169–184 (2012). doi:10.1016/j.biotechadv.2011.08.001

    Article  CAS  Google Scholar 

  30. G. Vitale, C.H. van Eijck, P.M. van Koetsveld Ing, J.L. Erdmann, E.J. Speel, K. van der Wansem Ing, D.M. Mooij, A. Colao, G. Lombardi, E. Croze, S.W. Lamberts et al., Type I interferons in the treatment of pancreatic cancer: mechanisms of action and role of related receptors. Ann. Surg. 246, 259–268 (2007). doi:10.1097/01.sla.0000261460.07110.f2

    Article  PubMed  PubMed Central  Google Scholar 

  31. F. Esposito, S. Libertini, R. Franco, A. Abagnale, L. Marra, G. Portella, P. Chieffi, Aurora B expression in post-puberal testicular germ cell tumours. J. Cell. Physiol. 221, 435–439 (2009). doi:10.1002/jcp.21875

    Article  PubMed  CAS  Google Scholar 

  32. F. Esposito, F. Boscia, R. Franco, M. Tornincasa, A. Fusco, S. Kitazawa, L.H. Looijenga, P. Chieffi, Down-regulation of estrogen receptor-β associates with transcriptional co-regulator PATZ1 delocalization in human testicular seminomas. J. Pathol. 224, 110–120 (2011). doi:10.1002/path.2846

    Article  PubMed  CAS  Google Scholar 

  33. M.E. Cabanillas, M.I. Hu, C. Jimenez, Medullary thyroid cancer in the era of tyrosine kinase inhibitors: to treat or not to treat-and with which drug-those are the questions. J. Clin. Endocrinol. Metab. 99, 4390–4396 (2014). doi:10.1210/jc.2014-2811

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Y.M. Cheng, Q. Zhu, Y.Y. Yao, Y. Tang, M.M. Wang, L.F. Zou, 8-Chloroadenosine 3′,5′-monophosphate induces cell cycle arrest and apoptosis in multiple myeloma cells through multiple mechanisms. Oncol. Lett. 4, 1384–1388 (2012). doi:10.3892/ol.2012.905

    PubMed  PubMed Central  CAS  Google Scholar 

  35. G. Tortora, F. Ciardiello, S. Pepe, P. Tagliaferri, A. Ruggiero, C. Bianco, R. Guarrasi, K. Miki, A.R. Bianco, Phase I clinical study with 8-chloro-cAMP and evaluation of immunological effects in cancer patients. Clin. Cancer Res. 1, 377–384 (1995)

    PubMed  CAS  Google Scholar 

  36. J.H. Han, Y.H. Ahn, K.Y. Choi, S.H. Hong, Involvement of AMP-activated protein kinase and p38 mitogen-activated protein kinase in 8-Cl-cAMP-induced growth inhibition. J. Cell. Physiol. 218, 104–112 (2009). doi:10.1002/jcp.21573

    Article  PubMed  CAS  Google Scholar 

  37. C.M. Stellrecht, H.V. Vangapandu, X.F. Le, W. Mao, S. Shentu, ATP directed agent, 8-chloro-adenosine, induces AMP activated protein kinase activity, leading to autophagic cell death in breast cancer cells. J. Hematol. Oncol. Pharm. 7, 23 (2014). doi:10.1186/1756-8722-7-23

    Article  CAS  Google Scholar 

  38. Y.S. Cho-Chung, M.V. Nesterova, Tumor reversion: protein kinase A isozyme switching. Ann. NY. Acad. Sci. 1058, 76–86 (2005). doi:10.1196/annals.1359.014

    Article  PubMed  CAS  Google Scholar 

  39. S.N. Kim, S.G. Kim, J.H. Park, M.A. Lee, S.D. Park, Y.S. Cho-Chung, S.H. Hong, Dual anticancer activity of 8-Cl-cAMP: inhibition of cell proliferation and induction of apoptotic cell death. Biochem. Biophys. Res. Commun. 5(273), 404–410 (2000). doi:10.1006/bbrc.2000.2949

    Article  CAS  Google Scholar 

  40. S.N. Kim, Y.H. Ahn, S.G. Kim, S.D. Park, Y.S. Cho-Chung, S.H. Hong, 8-Cl-cAMP induces cell cycle-specific apoptosis in human cancer cells. Int. J. Cancer 93, 33–41 (2001). doi:10.1002/ijc.1308

    Article  PubMed  CAS  Google Scholar 

  41. D. Calebiro, T. de Filippis, S. Lucchi, F. Martinez, P. Porazzi, R. Trivellato, M. Locati, P. Beck-Peccoz, L. Persani, Selective modulation of protein kinase A I and II reveals distinct roles in thyroid cell gene expression and growth. Mol. Endocrinol. 20, 3196–3211 (2006). doi:10.1210/me.2005-0493

    Article  PubMed  CAS  Google Scholar 

  42. L.A. Cass, S.A. Summers, G.V. Prendergast, J.M. Backer, M.J. Birnbaum, J.L. Meinkoth, Protein kinase A-dependent and -independent signaling pathways contribute to cyclic AMP-stimulated proliferation. Mol. Cell. Biol. 19, 5882–5891 (1999)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. P.J. Rogue, J.P. Humbert, A. Meyer, S. Freyermuth, M.M. Krady, A.N. Malviya, cAMP-dependent protein kinase phosphorylates and activates nuclear Ca2+-ATPase. PNAS 95, 9178–9183 (1998)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. I.H. Heijink, H.F. Kauffman, D.S. Postma, J.G. de Monchy, E. Vellenga, Sensitivity of IL-5 production to the cAMP-dependent pathway in human T cells is reduced by exogenous IL-2 in a phosphoinositide 3-kinase-dependent way. Eur. J. Immunol. 33, 2206–2215 (2003). doi:10.1002/eji.200323804

    Article  PubMed  CAS  Google Scholar 

  45. M. David, E. Petricoin III, A.C. Larner, Activation of protein kinase A inhibits interferon induction of the Jak/Stat pathway in U266 cells. J. Biol. Chem. 271, 4585–4588 (1996). doi:10.1074/jbc.271.9.4585

    Article  PubMed  CAS  Google Scholar 

  46. S.J. Cook, F. McCormick, Inhibition by cAMP of Ras-dependent activation of Raf. Science 262, 1069–1072 (1993). doi:10.1126/science.7694367

    Article  PubMed  CAS  Google Scholar 

  47. C.F. Ibáñez, Structure and physiology of the RET receptor tyrosine kinase. Cold Spring Harb. Perspect. Biol. 1, 5 (2013). doi:10.1101/cshperspect.a009134

    Google Scholar 

  48. T. Fukuda, K. Kiuchi, M. Takahashi, Novel mechanism of regulation of Rac activity and lamellipodia formation by RET tyrosine kinase. J. Biol. Chem. 24, 19114–19121 (2002). doi:10.1074/jbc.M200643200

    Article  CAS  Google Scholar 

  49. M. Perrinjaquet, M. Vilar, C.F. Ibáñez, Protein-tyrosine phosphatase SHP2 contributes to GDNF neurotrophic activity through direct binding to phospho-Tyr687 in the RET receptor tyrosine kinase. J. Biol. Chem. 285, 31867–31875 (2010). doi:10.1074/jbc.M110.144923

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. S. Pepe, G. Tortora, P.D. Noguchi, G.E. Marti, G.C. Washington, Y.S. Cho-Chung, Effects of 8-chloroadenosine 3′,5′-monophosphate and N6-benzyl-cyclic adenosine 5′-monophosphate on cell cycle kinetics of HL-60 leukemia cells. Cancer Res. 51, 6263–6267 (1991)

    PubMed  CAS  Google Scholar 

  51. A.J. Robinson-White, H.P. Hsiao, W.W. Leitner, E. Greene, A. Bauer, N.L. Krett, M. Nesterova, C.A. Stratakis, Protein kinase A-independent inhibition of proliferation and induction of apoptosis in human thyroid cancer cells by 8-Cl-adenosine. J. Clin. Endocrinol. Metab. 93, 1020–1029 (2008). doi:10.1210/jc.2007-2331

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. S. Naviglio, A. Spina, M. Marra, A. Sorrentino, E. Chiosi, M. Romano, S. Improta, A. Budillon, G. Illiano, A. Abbruzzese et al., Adenylate cyclase/cAMP pathway downmodulation counteracts apoptosis induced by IFN-alpha in human epidermoid cancer cells. J. Interferon Cytokine Res. 27, 129–136 (2007). doi:10.1089/jir.2006.0101

    Article  PubMed  CAS  Google Scholar 

  53. S. Naviglio, M. Caraglia, A. Abbruzzese, E. Chiosi, D. Di Gesto, M. Marra, M. Romano, A. Sorrentino, L. Sorvillo, A. Spina et al., Protein kinase A as a biological target in cancer therapy. Expert. Opin. Ther. Tar. 13, 83–92 (2009). doi:10.1517/14728220802602349

    Article  CAS  Google Scholar 

  54. Y.A. Lazebnik, S.H. Kaufmann, S. Desnoyers, G.G. Poirier, W.C. Earnshaw, Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE. Nature 371, 346–347 (1994). doi:10.1038/371346a0

    Article  PubMed  CAS  Google Scholar 

  55. P.A. Henkart, S.J. Grinstein, Apoptosis: mitochondria resurrected? J. Exp. Med. 183, 1293–1295 (1996). doi:10.1084/jem.183.4.1293

    Article  PubMed  CAS  Google Scholar 

  56. S. Elmore, Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35, 495–516 (2007). doi:10.1080/01926230701320337

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. X.W. Meng, B.D. Koh, J.S. Zhang, K.S. Flatten, P.A. Schneider, D.D. Billadeau, A.D. Hess, B.D. Smith, J.E. Karp, S.H. Kaufmann, Poly(ADP-ribose) polymerase inhibitors sensitize cancer cells to death receptor-mediated apoptosis by enhancing death receptor expression. J. Biol. Chem. 289, 20543–20558 (2014). doi:10.1074/jbc.M114.549220

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. A.I. Scovassi, M. Denegri, M. Donzelli, L. Rossi, R. Bernardi, A. Mandarino, I. Frouin, C. Negri, Poly(ADP-ribose) synthesis in cells undergoing apoptosis: an attempt to face death before PARP degradation. Eur. J. Histochem. 42, 251–258 (1998)

    PubMed  CAS  Google Scholar 

  59. A.I. Scovassi, G.G. Poirier, Poly(ADP-ribosylation) and apoptosis. Mol. Cell. Biochem. 199, 125–137 (1999). doi:10.1023/A:1006962716377

    Article  PubMed  CAS  Google Scholar 

  60. D. Le Roith, M. Parrizas, V.A. Blakesley, The insulin-like growth factor-I receptor and apoptosis. Endocrine 7, 103–105 (1997). doi:10.1007/BF02778074

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was partially supported by the Italian Ministry of Education, Research and University (FIRB RBAP11884 M) and by Rusconi Foundation (PhD grant to E.S.G.).

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Authors and Affiliations

  1. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Via Zucchi 18, Cusano Milanino, 20095, Milan, Italy

    Alessandra Dicitore, Maria Orietta Borghi, Luca Persani & Giovanni Vitale

  2. Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy

    Elisa Stellaria Grassi, Maria Orietta Borghi, Germano Gaudenzi, Luca Persani & Giovanni Vitale

  3. Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy

    Michele Caraglia

  4. Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands

    Leo J. Hofland

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  1. Alessandra Dicitore
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Dicitore, A., Grassi, E.S., Caraglia, M. et al. The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines. Endocrine 51, 101–112 (2016). https://doi.org/10.1007/s12020-015-0597-7

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