Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update

Abstract

Pituitary tumor-transforming gene (PTTG) was only recently discovered. Its overexpression occurs in a wide variety of endocrine and non-endocrine tumors, including ones of pituitary, thyroid, ovary, breast, prostate, lung, esophagus, colon, and the central nervous system. It affects tumor invasiveness and recurrence in several systems, functions as a securin during cell cycle progression, and inhibits premature sister chromatid separation. PTTG is involved in multiple cellular pathways, including proliferation, DNA repair, transformation, angiogenesis induction, invasion, and the induction of genetic instability. In thyroid carcinomas, PTTG expression is a marker of invasiveness. PTTG is overexpressed in most pituitary adenomas, where it appears to correlate with recurrence and angiogenesis. Increasing evidence also points to the role of PTTG in endocrine organ development. For example, PTTG knockout mice show defective pancreatic b-cell proliferation. Herein, we review the current knowledge regarding PTTG-mediated pathways based on evidence from in vivo and in vitro studies as well as knockout mice models. We also summarize the issue of PTTG expression and its correlation with clinicopathologic parameters in patients with neoplasms, particularly of endocrine organs. In addition, we discuss in vitro and in vivo therapeutic models targeting PTTG overexpression.

CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer

“…We show for the first time that the effect of CDC23 knockdown on cellular proliferation could be reversed by the simultaneous knockdown of cyclin B1 and securin. This finding suggests that the effect of CDC23 is mediated, at least in part, by cyclin B1 and securin which is consistent with the role of these two proteins in cancer progression (Bowers & Boylan 2004, Borlak et al 2005, Winnepenninckx et al 2006, Salehi et al 2008.…”

ShRNA-mediated knockdown of pituitary tumor transforming gene 1 (PTTG1): optimization of the effect on early osteoblast differentiation

“…The PTTG family includes PTTG1, PTTG2, and PTTG3 [37,41]. Human PTTG1 gene is located on chromosome 5 and encodes Securin -a protein consisting of 202 amino acids (22 kDa) [41].…”

“…In human, PTTG1 exhibits 91 and 89 % amino acid sequence homology with PTTG2 and PTTG3, respectively [33]. PTTG1 is the most abundant and widely studied form of the substance [37]. Both PTTG1 gene inactivation and its excessive expression lead to the appearance of aneuploid cells [28].…”

“…PTTG1 is implicated in several normal cellular processes, including DNA damage repair, apoptosis, and angiogenesis. It also interacts with a number of factors both in vivo and in vitro [28,37]. PTTG1 also possesses trans-activating action and induces upregulation of several other genes [37].…”

“…While differential PTTG1 localization may be due to the variations in cell lines and tumor types examined, cell cycledependent expression of PTTG1 gene may also account for the reported differences. Translocation of PTTG1 from cytoplasm to nucleus might be mediated by the PTTG-binding factor (PBF) which contains a nuclear localization signal [4,37].…”