Subscribe to RSS
DOI: 10.1055/s-0029-1215588
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
Transcripts of PTTG and Growth Factors bFGF and IGF-1 are Correlated in Pituitary Adenomas
Publication History
received 22.10.2008
first decision 22.01.2009
accepted 11.03.2009
Publication Date:
26 May 2009 (online)
Abstract
The reasons for the increase of pituitary tumor-transforming gene (PTTG) transcripts in about 90% of pituitary adenomas are still not fully understood, although upregulation by basic fibroblast growth factor (bFGF) has been discussed as a potential cause. A possible influence of the Insulin like Growth Factor 1 (IGF-1) might be of interest, since this protein is also synthesized in most pituitary adenomas. Moreover, the principal regulation of the PTTG gene by IGF-1 and Insulin has been demonstrated in astrocytoma and breast cancer cells. We analyzed a large group (103 patients) of unselected clinical pituitary adenoma samples. From total RNA of frozen tumor samples (all subtypes) cDNA (complementary DNA) was synthesized and transcripts of PTTG, bFGF, IGF-1 were measured by Real-Time-PCR. Not only mRNA (messenger RNA) levels of bFGF, but also of IGF-1, correlated strongly with PTTG transcripts. This result was obtained, when all pituitary adenoma samples were included in the statistical calculations, irrespective of their subclassification. Our study suggests a connection between PTTG and IGF-1 in pituitary adenomas.
Key words
pituitary adenoma - PTTG - bFGF - IGF-1 - real-time PCR
References
- 1 Baird A, Mormède P, Ying SY. et al . A nonmitogenic pituitary function of fibroblast growth factor: regulation of thyrotropin and prolactin secretion. Proc Natl Acad Sci USA. 1985; 82 5545-5549
- 2 Castillo AI, Tolon RM, Aranda A. Insulin-like growth factor-1 stimulates rat prolactin gene expression by a Ras, ETS and phosphatidylinositol 3-kinase dependent mechanism. Oncogene. 1998; 16 1981-1991
- 3 Chamaon K, Kirches E, Kanakis D. et al . Regulation of the pituitary tumor transforming gene by insulin-like growth factor-I and insulin differs between malignant and non-neoplastic astrocytes. Biochem Biophys Res Commun. 2005; 331 ((1)) 86-92
- 4 Chien W, Pei L. A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product. J Biol Chem. 2000; 275 19422-19427
- 5 Heaney AP, Horwitz GA, Wang Z. et al . Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis. Nat Med. 1999; 5 1317-1321
- 6 Heaney AP, Fernando M, Melmed S. Functional role of estrogen in pituitary tumor pathogenesis. J Clin Invest. 2002; 109 277-283
- 7 Horwitz GA, Miklovsky I, Heaney AP. et al . Human pituitary tumor-transforming gene (PTTG1) motif suppresses prolactin expression. Mol Endocrinol. 2003; 17 600-609
- 8 Ishikawa H, Heaney AP, Yu R. et al . Human pituitary tumor-transforming gene induces angiogenesis. J Clin Endocrinol Metab. 2001; 86 867-874
- 9 Kanakis D, Kirches E, Mawrin C. et al . Promoter mutations are no major cause of PTTG overexpression in pituitary adenomas. Clin Endocrinol (Oxf). 2003; 58 151-155
- 10 Karga HJ, Alexander JM, Hedley-Whyte ET. et al . Ras mutations in human pituitary tumors. J Clin Endocrinol Metab. 1992; 74 914-919
- 11 LeRoith D, Baserga R, Helman L. et al . Insulin-like growth factors and cancer. Ann Intern Med. 1995; 122 54-59
- 12 Lyons J, Landis CA, Harsh G. et al . Two G protein oncogenes in human endocrine tumors. Science. 1990; 249 655-659
- 13 McCabe CJ, Khaira JS, Boelaert K. et al . Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor-2 (FGF-2) in human pituitary adenomas: relationships to clinical tumour behaviour. Clin Endocrinol (Oxf). 2003; 58 141-150
- 14 Minematsu T, Suzuki M, Sanno N. et al . PTTG overexpression is correlated with angiogenesis in human pituitary adenomas. Endocr Pathol. 2006; 17 143-153
- 15 Moschos SJ, Mantzoros CS. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology. 2002; 63 317-332
- 16 Otsuka F, Tamiya T, Yamauchi T. et al . Quantitative analysis of growth-related factors in human pituitary adenomas. Lowered insulin-like growth factor-I and its receptor mRNA in growth hormone-producing adenomas. Regul Pept. 1999; 83 31-38
- 17 Pei L, Melmed S, Scheithauer B. et al . H-ras mutations in human pituitary carcinoma metastases. J Clin Endocrinol Metab. 1994; 78 842-846
- 18 Pei L, Melmed S. Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1997; 11 433-441
- 19 Pei L. Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function. J Biol Chem. 2000; 275 31191-31198
- 20 Piecha G, Chudek J, Wiecek A. Multiple Endocrine Neoplasia type 1. Eur J Intern Med. 2008; 19 99-103
- 21 Sandberg AC, Engberg C, Lake M. et al . The expression of insulin-like growth factor I and insulin-like growth factor II genes in the human fetal and adult brain and in glioma. Neurosci Lett. 1988; 93 114-119
- 22 Schweppe RE, Frazer-Abel AA, Gutierrez-Hartmann A. et al . Functional components of fibroblast growth factor (FGF) signal transduction in pituitary cells. Identification of FGF response elements in the prolactin gene. J Biol Chem. 1997; 272 30852-30859
- 23 Thompson 3rd AD, Kakar SS. Insulin and IGF-1 regulate the expression of the pituitary tumor transforming gene (PTTG) in breast tumor cells. FEBS Lett. 2005; 579 3195-3200
- 24 Trojan LA, Kopinski P, Wei MX. et al . IGF-I: from diagnostic to triple-helix gene therapy of solid tumors. Acta Biochim Pol. 2002; 49 979-990
- 25 Vallar L, Spada A, Giannattasio G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature. 1987; 330 566-568
- 26 Wang L, Adamo ML. Cell density influences insulin-like growth factor I gene expression in a cell type-specific manner. Endocrinology. 2000; 141 2481-2489
- 27 Widhalm G, Woflsberger S, Preusser M. et al . O(6)-methylguanine DNA methyltransferase immunoexpression in nonfunctioning pituitary adenomas: are progressive tumors potential candidates for temozolomide treatment?. Cancer. 2009; , [epub ahead of print]
- 28 Wierinckx A, Auger C, Devauchelle P. et al . A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors. Endocr Relat Cancer. 2007; 14 887-900
- 29 Woloschak M, Roberts JL, Post K. c-myc, c-fos, and c-myb gene expression in human pituitary adenomas. J Clin Endocrinol Metab. 1994; 79 253-257
- 30 Yamada S, Takada K. Angiogenesis in pituitary adenomas. Microsc Res Tech. 2003; 60 236-243
- 31 Yong Y, Tan Y, Zhou C. et al . Pituitary tumor transforming gene interacts with SP1 to modulate G1/S cell phase transition. Oncogene. 2007; 26 5596-5605
- 32 Zhang X, Horwitz GA, Prezant TR. et al . Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 1999; 13 156-166
- 33 Zhang X, Horwitz GA, Heaney AP. et al . Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab. 1999; 84 761-767
- 34 Zhu JL, Kaytor EN, Pao C-I. et al . Involvement of Sp1 in the transcriptional regulation of the rat insulin-like growth factor-I gene. Mol Cell Endocrinol. 2000; 164 205-218
Correspondence
D. KanakisMD, PhD
1st Department of Pathology
National and Kapodistrian University of Athens
Mikras Asias 75
11527 Athens
Greece
Phone: +0030/210/746 22 29
Fax: +0030/210/746 21 57
Email: aristoteles_stageira@yahoo.com