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Pituitary Tumors: Role of Pituitary Tumor-Transforming Gene-1 (PTTG1)

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Tumors of the Central Nervous System, Volume 10

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 10))

Abstract

Human pituitary tumor transforming gene-1 (PTTG1) is a novel oncogene. Its overexpression occurs in a wide variety of human tumors including pituitary adenomas. Several factors and signalling pathways regulate pituitary PTTG1 expression, including estrogen, epidermal growth factor, octamer-binding transcription factor 1 and Rb/E2F1. PTTG1 is extensively involved in physiologic and oncogenic functions. Molecular and clinical studies implicate diverse roles of PTTG1 in cell cycle regulation, genetic instability, cell proliferation, pituitary tumor angiogenesis and senescence. Both transgenic and knockout mouse models support a causal role for PTTG1 in the development of pituitary tumors. Here, we review the current knowledge of the regulatory mechanisms and the biological and pathophysiological roles of PTTG1 in pituitary tumors.

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References

  • Abbud RA, Takumi I, Barker EM, Ren SG, Chen DY, Wawrowsky K, Melmed S (2005) Early multipotential pituitary focal hyperplasia in the alpha-subunit of glycoprotein hormone-driven pituitary tumor-transforming gene transgenic mice. Mol Endocrinol 19:1383–1391

    Article  PubMed  CAS  Google Scholar 

  • Boelaert K, Yu R, Tannahill LA, Stratford AL, Khanim FL, Eggo MC, Moore JS, Young LS, Gittoes NJ, Franklyn JA, Melmed S, McCabe CJ (2004) PTTG’s C-terminal PXXP motifs modulate critical cellular processes in vitro. J Mol Endocrinol 33:663–677

    Article  PubMed  CAS  Google Scholar 

  • Chamaon K, Kirches E, Kanakis D, Braeuninger S, Dietzmann K, Mawrin C (2005) 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 331:86–92

    Article  PubMed  CAS  Google Scholar 

  • Chen L, Puri R, Lefkowitz EJ, Kakar SS (2000) Identification of the human pituitary tumor transforming gene (hPTTG) family: molecular structure, expression, and chromosomal localization. Gene 248:41–50

    Article  PubMed  CAS  Google Scholar 

  • Chesnokova V, Kovacs K, Castro AV, Zonis S, Melmed S (2005) Pituitary hypoplasia in pttg-/- mice is protective for Rb+/− pituitary tumorigenesis. Mol Endocrinol 19:2371–2379

    Article  PubMed  CAS  Google Scholar 

  • Chesnokova V, Zonis S, Rubinek T, Yu R, Ben-Shlomo A, Kovacs K, Wawrowsky K, Melmed S (2007) Senescence mediates pituitary hypoplasia and restrains pituitary tumor growth. Cancer Res 67:10564–10572

    Article  PubMed  CAS  Google Scholar 

  • Chesnokova V, Zonis S, Kovacs K, Ben-Shlomo A, Wawrowsky K, Bannykh S, Melmed S (2008) p21(Cip1) restrains pituitary tumor growth. Proc Natl Acad Sci USA 105:17498–17503

    Article  PubMed  CAS  Google Scholar 

  • Chien W, Pei L (2000) A novel binding factor facilitates nuclear translocation and transcriptional activation function of the pituitary tumor-transforming gene product. J Biol Chem 275:19422–19427

    Article  PubMed  CAS  Google Scholar 

  • Dominguez A, Ramos-Morales F, Romero F, Rios RM, Dreyfus F, Tortolero M, Pintor-Toro JA (1998) hpttg, a human homologue of rat pttg, is overexpressed in hematopoietic neoplasms. Evidence for a transcriptional activation function of hPTTG. Oncogene 17:2187–2193

    Article  PubMed  CAS  Google Scholar 

  • Donangelo I, Gutman S, Horvath E, Kovacs K, Wawrowsky K, Mount M, Melmed S (2006) Pituitary tumor transforming gene overexpression facilitates pituitary tumor development. Endocrinology 147:4781–4791

    Article  PubMed  CAS  Google Scholar 

  • Filippella M, Galland F, Kujas M, Young J, Faggiano A, Lombardi G, Colao A, Meduri G, Chanson P (2006) Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study. Clin Endocrinol (Oxf) 65:536–543

    Article  Google Scholar 

  • Heaney AP, Horwitz GA, Wang Z, Singson R, Melmed S (1999) Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis. Nat Med 5:1317–1321

    Article  PubMed  CAS  Google Scholar 

  • Heaney AP, Fernando M, Melmed S (2002) Functional role of estrogen in pituitary tumor pathogenesis. J Clin Invest 109:277–283

    PubMed  CAS  Google Scholar 

  • Hunter JA, Skelly RH, Aylwin SJ, Geddes JF, Evanson J, Besser GM, Monson JP, Burrin JM (2003) The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas. Eur J Endocrinol 148:203–211

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa H, Heaney AP, Yu R, Horwitz GA, Melmed S (2001) Human pituitary tumor-transforming gene induces angiogenesis. J Clin Endocrinol Metab 86:867–874

    Article  PubMed  CAS  Google Scholar 

  • Jallepalli PV, Waizenegger IC, Bunz F, Langer S, Speicher MR, Peters JM, Kinzler KW, Vogelstein B, Lengauer C (2001) Securin is required for chromosomal stability in human cells. Cell 105:445–457

    Article  PubMed  CAS  Google Scholar 

  • Lee UE, Ghiassi-Nejad Z, Paris AJ, Yea S, Narla G, Walsh M, Friedman SL (2010) Tumor suppressor activity of KLF6 mediated by downregulation of the PTTG1 oncogene. FEBS Lett 584:1006–1010

    Article  PubMed  CAS  Google Scholar 

  • Marangos P, Carroll J (2008) Securin regulates entry into M-phase by modulating the stability of cyclin B. Nat Cell Biol 10:445–451

    Article  PubMed  CAS  Google Scholar 

  • McCabe CJ, Boelaert K, Tannahill LA, Heaney AP, Stratford AL, Khaira JS, Hussain S, Sheppard MC, Franklyn JA, Gittoes NJ (2002) Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors. J Clin Endocrinol Metab 87:4238–4244

    Article  PubMed  CAS  Google Scholar 

  • McCabe CJ, Khaira JS, Boelaert K, Heaney AP, Tannahill LA, Hussain S, Mitchell R, Olliff J, Sheppard MC, Franklyn JA, Gittoes NJ (2003) 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) 58:141–150

    Article  CAS  Google Scholar 

  • Minematsu T, Suzuki M, Sanno N, Takekoshi S, Teramoto A, Osamura RY (2006) PTTG overexpression is correlated with angiogenesis in human pituitary adenomas. Endocr Pathol 17:143–153

    Article  PubMed  CAS  Google Scholar 

  • Mu YM, Oba K, Yanase T, Ito T, Ashida K, Goto K, Morinaga H, Ikuyama S, Takayanagi R, Nawata H (2003) Human pituitary tumor transforming gene (hPTTG) inhibits human lung cancer A549 cell growth through activation of p21(WAF1/CIP1). Endocr J 50:771–781

    Article  PubMed  CAS  Google Scholar 

  • Pei L (2000) Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function. J Biol Chem 275:31191–31198

    Article  PubMed  CAS  Google Scholar 

  • Pei L (2001) Identification of c-myc as a down-stream target for pituitary tumor-transforming gene. J Biol Chem 276:8484–8491

    Article  PubMed  CAS  Google Scholar 

  • Pei L, Melmed S (1997) Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol 11:433–441

    Article  PubMed  CAS  Google Scholar 

  • Ramos-Morales F, Dominguez A, Romero F, Luna R, Multon MC, Pintor-Toro JA, Tortolero M (2000) Cell cycle regulated expression and phosphorylation of hpttg proto-oncogene product. Oncogene 19:403–409

    Article  PubMed  CAS  Google Scholar 

  • Romero F, Multon MC, Ramos-Morales F, Dominguez A, Bernal JA, Pintor-Toro JA, Tortolero M (2001) Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase. Nucleic Acids Res 29:1300–1307

    Article  PubMed  CAS  Google Scholar 

  • Saez C, Japon MA, Ramos-Morales F, Romero F, Segura DI, Tortolero M, Pintor-Toro JA (1999) hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias. Oncogene 18:5473–5476

    Article  PubMed  CAS  Google Scholar 

  • Stratford AL, Boelaert K, Tannahill LA, Kim DS, Warfield A, Eggo MC, Gittoes NJ, Young LS, Franklyn JA, McCabe CJ (2005) Pituitary tumor transforming gene binding factor: a novel transforming gene in thyroid tumorigenesis. J Clin Endocrinol Metab 90:4341–4349

    Article  PubMed  CAS  Google Scholar 

  • Tong Y, Tan Y, Zhou C, Melmed S (2007) Pituitary tumor transforming gene interacts with Sp1 to modulate G1/S cell phase transition. Oncogene 26:5596–5605

    Article  PubMed  CAS  Google Scholar 

  • Vlotides G, Cruz-Soto M, Rubinek T, Eigler T, Auernhammer CJ, Melmed S (2006) Mechanisms for growth factor-induced pituitary tumor transforming gene-1 expression in pituitary folliculostellate TtT/GF cells. Mol Endocrinol 20:3321–3335

    Article  PubMed  CAS  Google Scholar 

  • Vlotides G, Eigler T, Melmed S (2007) Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. Endocr Rev 28:165–186

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Yu R, Melmed S (2001) Mice lacking pituitary tumor transforming gene show testicular and splenic hypoplasia, thymic hyperplasia, thrombocytopenia, aberrant cell cycle progression, and premature centromere division. Mol Endocrinol 15:1870–1879

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Moro E, Kovacs K, Yu R, Melmed S (2003) Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes. Proc Natl Acad Sci USA 100:3428–3432

    Article  PubMed  CAS  Google Scholar 

  • Wierinckx A, Auger C, Devauchelle P, Reynaud A, Chevallier P, Jan M, Perrin G, Fevre-Montange M, Rey C, Figarella-Branger D, Raverot G, Belin MF, Lachuer J, Trouillas J (2007) A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors. Endocr Relat Cancer 14:887–900

    Article  PubMed  CAS  Google Scholar 

  • Yin H, Fujimoto N, Maruyama S, Asano K (2001) Strain difference in regulation of pituitary tumor transforming gene (PTTG) in estrogen-induced pituitary tumorigenesis in rats. Jpn J Cancer Res 92:1034–1040

    Article  PubMed  CAS  Google Scholar 

  • Yu R, Ren SG, Horwitz GA, Wang Z, Melmed S (2000) Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division and survival: evidence from live cell imaging. Mol Endocrinol 14:1137–1146

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S (1999a) Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 84:761–767

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Horwitz GA, Prezant TR, Valentini A, Nakashima M, Bronstein MD, Melmed S (1999b) Structure, expression, and function of human pituitary tumor-transforming gene (PTTG). Mol Endocrinol 13:156–166

    Article  PubMed  CAS  Google Scholar 

  • Zhou C, Tong Y, Wawrowsky K, Bannykh S, Donangelo I, Melmed S (2008) Oct-1 induces pituitary tumor transforming gene expression in endocrine tumors. Endocr Relat Cancer 15:817–831

    Article  PubMed  CAS  Google Scholar 

  • Zhou C, Wawrowsky K, Bannykh S, Gutman S, Melmed S (2009) E2F1 induces pituitary tumor transforming gene (PTTG1) expression in human pituitary tumors. Mol Endocrinol 23:2000–2012

    Article  PubMed  CAS  Google Scholar 

  • Zou H, McGarry TJ, Bernal T, Kirschner MW (1999) Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285:418–422

    Article  PubMed  CAS  Google Scholar 

  • Zur A, Brandeis M (2001) Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis. EMBO J 20:792–801

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, CA, 90048, USA

    Cuiqi Zhou

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  1. Cuiqi Zhou
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Correspondence to Cuiqi Zhou .

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  1. , Kean University, Room 213, Library building, Morris Avenue 1000, Union, 07083, New Jersey, USA

    M.A. Hayat

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Zhou, C. (2013). Pituitary Tumors: Role of Pituitary Tumor-Transforming Gene-1 (PTTG1). In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 10. Tumors of the Central Nervous System, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5681-6_22

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  • DOI: https://doi.org/10.1007/978-94-007-5681-6_22

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  • Online ISBN: 978-94-007-5681-6

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