Skip to main content

Advertisement

Log in

Analysis of differential gene expression in plurihormonal pituitary adenomas using bead-based fiber-optic arrays

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Plurihormonal pituitary adenomas (PHPAs) are defined as those pituitary adenomas secreting two or more hormones that differ in chemical composition, immunoreactivity, and biologic effects. Since the pathogenesis of these adenomas is not well understood, our study aimed to explore mechanisms underlying the pathogenesis of PHPAs. We used bead-based fiber-optic arrays (Illumina Human GeneChip WG-6 v3.0) to examine the gene expression profiles in seven PHPAs compared with three normal pituitary glands. Four differentially expressed genes were chosen randomly for validation by quantitative real-time reverse-transcription polymerase chain reaction. We then performed pathway analysis of all differentially expressed genes using the Kyoto Encyclopedia of Genes and Genomes. Our array analysis showed significant increases in the expression of 6 genes and decreases in 334 genes and 15 expressed sequence tags in the PHPAs. Bioinformatic analysis showed that genes HIGD1B, EPS8, ECT2, and BTG2 might play an important role in the tumorigenesis and progression of PHPAs. Pathway analysis showed that the p53 and Notch signaling pathways may play an important role in tumorigenesis and progression of PHPAs, and extracellular matrix (ECM)–receptor interactions likely play a role in the inhibition of invasion and metastasis in these tumors. Our data suggested that there are numerous aberrantly expressed genes and pathways involved in the pathogenesis of PHPAs. Bead-based fiber-optic arrays combined with pathway analysis of gene expression data appears to be a valid method for investigating the pathogenesis of tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Ho DM, Hsu CY, Ting LT, Chiang H (2001) Plurihormonal pituitary adenomas: immunostaining of all pituitary hormones is mandatory for correct classification. Histopathology 39:310–319

    Article  PubMed  CAS  Google Scholar 

  2. Kameya T, Furuhata S (1991) Plurihormonal adenomas. Analysis of 62 cases. Pathol Res Pract 187:574–576

    Article  PubMed  CAS  Google Scholar 

  3. Kageyama K, Nigawara T, Kamata Y, Terui K, Anzai J, Sakihara S, Suda T (2002) A multihormonal pituitary adenoma with growth hormone and adrenocorticotropic hormone production, causing acromegaly and Cushing disease. Am J Med Sci 324:326–330

    Article  PubMed  Google Scholar 

  4. Mao S, Dong G (2005) Discovery of highly differentiative gene groups from microarray gene expression data using the gene club approach. J Bioinform Comput Biol 3:1263–1280

    Article  PubMed  CAS  Google Scholar 

  5. Ellestad LE, Carre W, Muchow M, Jenkins SA, Wang X, Cogburn LA, Porter TE (2006) Gene expression profiling during cellular differentiation in the embryonic pituitary gland using cDNA microarrays. Physiol Genomics 25:414–425

    Article  PubMed  CAS  Google Scholar 

  6. Tarca AL, Romero R, Draghici S (2006) Analysis of microarray experiments of gene expression profiling. Am J Obstet Gynecol 195:373–388

    Article  PubMed  CAS  Google Scholar 

  7. Denko N, Schindler C, Koong A, Laderoute K, Green C, Giaccia A (2000) Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment. Clin Cancer Res 6:480–487

    PubMed  CAS  Google Scholar 

  8. Xu M, Shorts-Cary L, Knox AJ, Kleinsmidt-DeMasters B, Lillehei K, Wierman ME (2009) Epidermal growth factor receptor pathway substrate 8 is overexpressed in human pituitary tumors: role in proliferation and survival. Endocrinology 150:2064–2071

    Article  PubMed  CAS  Google Scholar 

  9. Miki T, Smith CL, Long JE, Eva A, Fleming TP (1993) Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature 362:462–465

    Article  PubMed  CAS  Google Scholar 

  10. Tatsumoto T, Xie X, Blumenthal R, Okamoto I, Miki T (1999) Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis. J Cell Biol 147:921–928

    Article  PubMed  CAS  Google Scholar 

  11. Petronczki M, Glotzer M, Kraut N, Peters JM (2007) Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Dev Cell 12:713–725

    Article  PubMed  CAS  Google Scholar 

  12. Sano M, Genkai N, Yajima N, Tsuchiya N, Homma J, Tanaka R, Miki T, Yamanaka R (2006) Expression level of ECT2 proto-oncogene correlates with prognosis in glioma patients. Oncol Rep 16:1093–1098

    PubMed  CAS  Google Scholar 

  13. Rouault JP, Falette N, Guehenneux F, Guillot C, Rimokh R, Wang Q, Berthet C, Moyret-Lalle C, Savatier P, Pain B, Shaw P, Berger R, Samarut J, Magaud JP, Ozturk M, Samarut C, Puisieux A (1996) Identification of BTG2, an antiproliferative p53-dependent component of the DNA damage cellular response pathway. Nat Genet 14:482–486

    Article  PubMed  CAS  Google Scholar 

  14. Cortes U, Moyret-Lalle C, Falette N, Duriez C, Ghissassi FE, Barnas C, Morel AP, Hainaut P, Magaud JP, Puisieux A (2000) BTG gene expression in the p53-dependent and -independent cellular response to DNA damage. Mol Carcinog 27:57–64

    Article  PubMed  CAS  Google Scholar 

  15. Farioli-Vecchioli S, Tanori M, Micheli L, Mancuso M, Leonardi L, Saran A, Ciotti MT, Ferretti E, Gulino A, Pazzaglia S, Tirone F (2007) Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3. FASEB J 21:2215–2225

    Article  PubMed  CAS  Google Scholar 

  16. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA 102:15545–15550

    Article  PubMed  CAS  Google Scholar 

  17. Paez-Pereda M, Kuchenbauer F, Arzt E, Stalla GK (2005) Regulation of pituitary hormones and cell proliferation by components of the extracellular matrix. Braz J Med Biol Res 38:1487–1494

    Article  PubMed  CAS  Google Scholar 

  18. Danen EH, Yamada KM (2001) Fibronectin, integrins, and growth control. J Cell Physiol 189:1–13

    Article  PubMed  CAS  Google Scholar 

  19. Huet C, Pisselet C, Mandon-Pepin B, Monget P, Monniaux D (2001) Extracellular matrix regulates ovine granulosa cell survival, proliferation and steroidogenesis: relationships between cell shape and function. J Endocrinol 169:347–360

    Article  PubMed  CAS  Google Scholar 

  20. Kuchenbauer F, Hopfner U, Stalla J, Arzt E, Stalla GK, Paez-Pereda M (2001) Extracellular matrix components regulate ACTH production and proliferation in corticotroph tumor cells. Mol Cell Endocrinol 175:141–148

    Article  PubMed  CAS  Google Scholar 

  21. Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284:770–776

    Article  PubMed  CAS  Google Scholar 

  22. Farnie G, Clarke RB, Spence K, Pinnock N, Brennan K, Anderson NG, Bundred NJ (2007) Novel cell culture technique for primary ductal carcinoma in situ: role of Notch and epidermal growth factor receptor signaling pathways. J Natl Cancer Inst 99:616–627

    Article  PubMed  CAS  Google Scholar 

  23. Stylianou S, Clarke RB, Brennan K (2006) Aberrant activation of notch signaling in human breast cancer. Cancer Res 66:1517–1525

    Article  PubMed  CAS  Google Scholar 

  24. Villaronga MA, Bevan CL, Belandia B (2008) Notch signaling: a potential therapeutic target in prostate cancer. Curr Cancer Drug Targets 8:566–580

    Article  PubMed  CAS  Google Scholar 

  25. Nakakura T, Sato M, Suzuki M, Hatano O, Takemori H, Taniguchi Y, Minoshima Y, Tanaka S (2009) The spatial and temporal expression of delta-like protein 1 in the rat pituitary gland during development. Histochem Cell Biol 131:141–153

    Article  PubMed  CAS  Google Scholar 

  26. Yevtodiyenko A, Schmidt JV (2006) Dlk1 expression marks developing endothelium and sites of branching morphogenesis in the mouse embryo and placenta. Dev Dyn 235:1115–1123

    Article  PubMed  CAS  Google Scholar 

  27. Bergman LM, Birts CN, Darley M, Gabrielli B, Blaydes JP (2009) CtBPs promote cell survival through the maintenance of mitotic fidelity. Mol Cell Biol 29:4539–4551

    Article  PubMed  CAS  Google Scholar 

  28. Raetzman LT, Cai JX, Camper SA (2007) Hes1 is required for pituitary growth and melanotrope specification. Dev Biol 304:455–466

    Article  PubMed  CAS  Google Scholar 

  29. Vogelstein B, Lane D, Levine AJ (2000) Surfing the p53 network. Nature 408:307–310

    Article  PubMed  CAS  Google Scholar 

  30. Gasco M, Shami S, Crook T (2002) The p53 pathway in breast cancer. Breast Cancer Res 4:70–76

    Article  PubMed  CAS  Google Scholar 

  31. Ying J, Srivastava G, Hsieh WS, Gao Z, Murray P, Liao SK, Ambinder R, Tao Q (2005) The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors. Clin Cancer Res 11:6442–6449

    Article  PubMed  CAS  Google Scholar 

  32. Ohki R, Nemoto J, Murasawa H, Oda E, Inazawa J, Tanaka N, Taniguchi T (2000) Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase. J Biol Chem 275:22627–22630

    Article  PubMed  CAS  Google Scholar 

  33. Pietenpol JA, Stewart ZA (2002) Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis. Toxicology 181–182:475–481

    Article  PubMed  Google Scholar 

  34. Kapoor S (2008) Altered expression of the PMAIP1 gene: a major player in the evolution of gastrointestinal and systemic malignancies. Dig Dis Sci 53:2834–2835

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yazhuo Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, Z., Gui, S. & Zhang, Y. Analysis of differential gene expression in plurihormonal pituitary adenomas using bead-based fiber-optic arrays. J Neurooncol 108, 341–348 (2012). https://doi.org/10.1007/s11060-011-0792-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-011-0792-1

Keywords

Navigation