Horm Metab Res 2011; 43(5): 325-330
DOI: 10.1055/s-0031-1271748
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Analysis of Differential Gene Expression by Bead-based Fiber-Optic Array in Nonfunctioning Pituitary Adenomas

Z. Jiang1 , S. Gui2 , Y. Zhang3
  • 1Capital Medical University; Beijing Neurosurgical Institute, Beijing, P. R. China
  • 2Neurosurgical Department, Beijing Tiantan Hospital, 6 Tiantan Xili, Dongcheng District, Beijing, P. R. China
  • 3Beijing Neurosurgical Institute, 6 Tiantan Xili, Dongcheng District, Beijing, P. R. China
Further Information

Publication History

received 14.09.2010

accepted 19.01.2011

Publication Date:
24 February 2011 (online)

Abstract

Nonfunctioning pituitary adenomas (NFPAs) are relatively common, accounting for 30% of all pituitary adenomas; however, their pathogenesis remains enigmatic. To explore the possible pathogenesis of NFPAs, we used fiber-optic BeadArray to examine gene expression in 5 NFPAs compared with 3 normal pituitaries. 4 differentially expressed genes were chosen randomly for validation by reverse transcriptase-real time quantitative polymerase chain reaction (RT-qPCR). We then analyzed the differentially expressed gene profile with Kyoto Encyclopedia of Genes and Genomes (KEGG). The array analysis indentified significant increases in the expression of 1 402 genes and 383 expressed sequence tags (ESTs), and decreases in 1 697 genes and 113 ESTs in the NFPAs. Bioinformatic and pathway analysis showed that the genes HIGD1B, FAM5C, PMAIP1 and the pathway cell-cycle regulation may play an important role in tumorigenesis and progression of NFPAs. Our data suggest fiber-optic BeadArray combined with pathway analysis of differential gene expression profile appears to be a valid approach for investigating the pathogenesis of tumors.

References

  • 1 Asa SL, Kovacs K. Clinically non-functioning human pituitary adenomas.  Can J Neurol Sci. 1992;  19 228-235
  • 2 Ferrante E, Ferraroni M, Castrignano T, Menicatti L, Anagni M, Reimondo G, Monte P, Bernasconi D, Loli P, Faustini-Fustini M, Borretta G, Terzolo M, Losa M, Morabito A, Spada A, Beck-Peccoz P, Lania AG. Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors.  Eur J Endocrinol. 2006;  155 823-829
  • 3 Dekkers OM, Pereira AM, Romijn JA. Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas.  J Clin Endocrinol Metab. 2008;  93 3717-3726
  • 4 Asa SL, Ezzat S. The cytogenesis and pathogenesis of pituitary adenomas.  Endocr Rev. 1998;  19 798-827
  • 5 Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S. Clonal origin of pituitary adenomas.  J Clin Endocrinol Metab. 1990;  71 1427-1433
  • 6 Simpson DJ, Bicknell JE, McNicol AM, Clayton RN, Farrell WE. Hypermethylation of the p16/CDKN2A/MTSI gene and loss of protein expression is associated with nonfunctional pituitary adenomas but not somatotrophinomas.  Genes Chromosomes Cancer. 1999;  24 328-336
  • 7 Gejman R, Batista DL, Zhong Y, Zhou Y, Zhang X, Swearingen B, Stratakis CA, Hedley-Whyte ET, Klibanski A. Selective loss of MEG3 expression and intergenic differentially methylated region hypermethylation in the MEG3/DLK1 locus in human clinically nonfunctioning pituitary adenomas.  J Clin Endocrinol Metab. 2008;  93 4119-4125
  • 8 Chaidarun SS, Eggo MC, Sheppard MC, Stewart PM. Expression of epidermal growth factor (EGF), its receptor, and related oncoprotein (erbB-2) in human pituitary tumors and response to EGF in vitro.  Endocrinology. 1994;  135 2012-2021
  • 9 Moreno CS, Evans CO, Zhan X, Okor M, Desiderio DM, Oyesiku NM. Novel molecular signaling and classification of human clinically nonfunctional pituitary adenomas identified by gene expression profiling and proteomic analyses.  Cancer Res. 2005;  65 10214-10222
  • 10 Evans CO, Young AN, Brown MR, Brat DJ, Parks JS, Neish AS, Oyesiku NM. Novel patterns of gene expression in pituitary adenomas identified by complementary deoxyribonucleic acid microarrays and quantitative reverse transcription-polymerase chain reaction.  J Clin Endocrinol Metab. 2001;  86 3097-3107
  • 11 Tateno T, Izumiyama H, Doi M, Yoshimoto T, Shichiri M, Inoshita N, Oyama K, Yamada S, Hirata Y. Differential gene expression in ACTH-secreting and non-functioning pituitary tumors.  Eur J Endocrinol. 2007;  157 717-724
  • 12 Galland F, Lacroix L, Saulnier P, Dessen P, Meduri G, Bernier M, Gaillard S, Guibourdenche J, Fournier T, Evain-Brion D, Bidart JM, Chanson P. Differential gene expression profiles of invasive and non-invasive non-functioning pituitary adenomas based on microarray analysis.  Endocr Relat Cancer. 2010;  17 361-371
  • 13 Evans CO, Moreno CS, Zhan X, McCabe MT, Vertino PM, Desiderio DM, Oyesiku NM. Molecular pathogenesis of human prolactinomas identified by gene expression profiling, RT-qPCR, and proteomic analyses.  Pituitary. 2008;  11 231-245
  • 14 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.  Methods. 2001;  25 402-408
  • 15 Denko N, Schindler C, Koong A, Laderoute K, Green C, Giaccia A. Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment.  Clin Cancer Res. 2000;  6 480-487
  • 16 Shorts-Cary L, Xu M, Ertel J, Kleinschmidt-Demasters BK, Lillehei K, Matsuoka I, Nielsen-Preiss S, Wierman ME. Bone morphogenetic protein and retinoic acid-inducible neural specific protein-3 is expressed in gonadotrope cell pituitary adenomas and induces proliferation, migration, and invasion.  Endocrinology. 2007;  148 967-975
  • 17 Kapoor S. Altered expression of the PMAIP1 gene: A major player in the evolution of gastrointestinal and systemic malignancies.  Dig Dis Sci. 2008;  53 2834-2835
  • 18 Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles.  Proc Natl Acad Sci USA. 2005;  102 15545-15550
  • 19 Bilodeau S, Roussel-Gervais A, Drouin J. Distinct developmental roles of cell cycle inhibitors p57Kip2 and p27Kip1 distinguish pituitary progenitor cell cycle exit from cell cycle reentry of differentiated cells.  Mol Cell Biol. 2009;  29 1895-1908
  • 20 Sherr CJ, Roberts JM. Living with or without cyclins and cyclin-dependent kinases.  Genes Dev. 2004;  18 2699-2711
  • 21 Tani Y, Inoshita N, Sugiyama T, Kato M, Yamada S, Shichiri M, Hirata Y. Upregulation of CDKN2A and suppression of cyclin D1 gene expressions in ACTH-secreting pituitary adenomas.  Eur J Endocrinol. 2010;  163 523-529
  • 22 Quereda V, Malumbres M. Cell cycle control of pituitary development and disease.  J Mol Endocrinol. 2009;  42 75-86
  • 23 Ramsey MR, Krishnamurthy J, Pei XH, Torrice C, Lin W, Carrasco DR, Ligon KL, Xiong Y, Sharpless NE. Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase 4/6-dependent tumors and tissues.  Cancer Res. 2007;  67 4732-4741
  • 24 Hossain MG, Iwata T, Mizusawa N, Qian ZR, Shima SW, Okutsu T, Yamada S, Sano T, Yoshimoto K. Expression of p18(INK4C) is down-regulated in human pituitary adenomas.  Endocr Pathol. 2009;  20 114-121
  • 25 Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer.  Nat Rev Cancer. 2001;  1 222-231
  • 26 Vlotides G, Eigler T, Melmed S. Pituitary tumor-transforming gene: physiology and implications for tumorigenesis.  Endocr Rev. 2007;  28 165-186
  • 27 Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas.  J Clin Endocrinol Metab. 1999;  84 761-767
  • 28 de Perez CI, de Carcer G, Malumbres M. A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy.  Carcinogenesis. 2007;  28 899-912

Correspondence

Z. JiangMD 

Beijing Neurosurgical Institute

6 Tiantan Xili

Dongcheng District

100050 Beijing

P. R. China

Phone: +86/10/670 22886

Fax: +86/10/670 57391

Email: zyz2004520@163.com