This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, R. Articles by Melmed, S. Search for Related Content PubMed PubMed Citation Articles by Yu, R. Articles by Melmed, S.

Pituitary Tumor Transforming Gene (PTTG) Regulates Placental JEG-3 Cell Division and Survival: Evidence from Live Cell Imaging

Division of Endocrinology Cedars-Sinai Research Institute-UCLA School of Medicine Los Angeles, California 90048

The pituitary transforming gene, PTTG, is abundantly expressed in endocrine neoplasms. PTTG has recently been recognized as a mammalian securin based on its biochemical homology to Pds1p. PTTG expression and intracellular localization were therefore studied during the cell cycle in human placental JEG-3 cells. PTTG mRNA and protein expressions were low at the G₁/S border, gradually increased during S phase, and peaked at G₂/M, but PTTG levels were attenuated as cells entered G₁. In interphase cells, wild-type PTTG, an epitope-tagged PTTG, and a PTTG-EGFP conjugate all localized to both the nucleus and cytoplasm, but in mitotic cells, PTTG was not observed in the chromosome region. PTTG-EGFP colocalized with mitotic spindles in early mitosis and was degraded in anaphase. Intracellular fates of PTTG-EGFP and a conjugate of EGFP and a mutant inactivated PTTG devoid of an SH3-binding domain were observed by real-time visualization of the EGFP conjugates in live cells. The same cells were continuously observed as they progressed from G₁/S border to S, G₂/M, and G₁. Most cells (67%) expressing PTTG-EGFP died by apoptosis, and few cells (4%) expressing PTTG-EGFP divided, whereas those expressing mutant PTTG-EGFP divided. PTTG-EGFP, as well as the mutant PTTG-EGFP, disappeared after cells divided. The results show that PTTG expression and localization are cell cycle-dependent and demonstrate that PTTG regulates endocrine tumor cell division and survival.

This article has been cited by other articles:

				V. Chesnokova, C. Wong, S. Zonis, A. Gruszka, K. Wawrowsky, S.-G. Ren, A. BenShlomo, and R. Yu Diminished Pancreatic {beta}-Cell Mass in Securin-Null Mice Is Caused by {beta}-Cell Apoptosis and Senescence Endocrinology, June 1, 2009; 150(6): 2603 - 2610. [Abstract] [Full Text] [PDF]

				F. Salehi, K. Kovacs, B. W Scheithauer, R. V Lloyd, and M. Cusimano Pituitary tumor-transforming gene in endocrine and other neoplasms: a review and update Endocr. Relat. Cancer, September 1, 2008; 15(3): 721 - 743. [Abstract] [Full Text] [PDF]

				C. S. Kim, H. Ying, M. C. Willingham, and S.-y. Cheng The pituitary tumor-transforming gene promotes angiogenesis in a mouse model of follicular thyroid cancer Carcinogenesis, May 1, 2007; 28(5): 932 - 939. [Abstract] [Full Text] [PDF]

				G. Vlotides, T. Eigler, and S. Melmed Pituitary Tumor-Transforming Gene: Physiology and Implications for Tumorigenesis Endocr. Rev., April 1, 2007; 28(2): 165 - 186. [Abstract] [Full Text] [PDF]

				D.S. Kim, J.A. Franklyn, V.E. Smith, A.L. Stratford, H.N. Pemberton, A. Warfield, J.C. Watkinson, T. Ishmail, M.J.O. Wakelam, and C.J. McCabe Securin induces genetic instability in colorectal cancer by inhibiting double-stranded DNA repair activity Carcinogenesis, March 1, 2007; 28(3): 749 - 759. [Abstract] [Full Text] [PDF]

				R. Yu, M. Cruz-Soto, S. L. Calzi, H. Hui, and S. Melmed Murine pituitary tumor-transforming gene functions as a securin protein in insulin-secreting cells. J. Endocrinol., October 1, 2006; 191(1): 45 - 53. [Abstract] [Full Text] [PDF]

				A. L. Stratford, K. Boelaert, L. A. Tannahill, D. S. Kim, A. Warfield, M. C. Eggo, N. J. L. Gittoes, L. S. Young, J. A. Franklyn, and C. J. McCabe Pituitary Tumor Transforming Gene Binding Factor: A Novel Transforming Gene in Thyroid Tumorigenesis J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4341 - 4349. [Abstract] [Full Text] [PDF]

				C. Cristina, G. Diaz-Torga, A. Baldi, A. Gongora, M. Rubinstein, M. J. Low, and D. Becu-Villalobos Increased Pituitary Vascular Endothelial Growth Factor-A in Dopaminergic D2 Receptor Knockout Female Mice Endocrinology, July 1, 2005; 146(7): 2952 - 2962. [Abstract] [Full Text] [PDF]

				K Boelaert, R Yu, L A Tannahill, A L Stratford, F L Khanim, M C Eggo, J S Moore, L S Young, N J L Gittoes, J A Franklyn, et al. PTTG's C-terminal PXXP motifs modulate critical cellular processes in vitro J. Mol. Endocrinol., December 1, 2004; 33(3): 663 - 677. [Abstract] [Full Text] [PDF]

				J. Tfelt-Hansen, S. Yano, S. Bandyopadhyay, R. Carroll, E. M. Brown, and N. Chattopadhyay Expression of Pituitary Tumor Transforming Gene (PTTG) and Its Binding Protein in Human Astrocytes and Astrocytoma Cells: Function and Regulation of PTTG in U87 Astrocytoma Cells Endocrinology, September 1, 2004; 145(9): 4222 - 4231. [Abstract] [Full Text] [PDF]

				R. Yu, W. Lu, J. Chen, C. J. McCabe, and S. Melmed Overexpressed Pituitary Tumor-Transforming Gene Causes Aneuploidy in Live Human Cells Endocrinology, November 1, 2003; 144(11): 4991 - 4998. [Abstract] [Full Text] [PDF]

				K. BOELAERT, L. A. TANNAHILL, J. N. BULMER, S. KACHILELE, S. Y. CHAN, D. KIM, N. J. L. GITTOES, J. A. FRANKLYN, M. D. KILBY, and C. J. MCCABE A potential role for PTTG/securin in the developing human fetal brain FASEB J, September 1, 2003; 17(12): 1631 - 1639. [Abstract] [Full Text] [PDF]

				G. A. Horwitz, I. Miklovsky, A. P. Heaney, S.-G. Ren, and S. Melmed Human Pituitary Tumor-Transforming Gene (PTTG1) Motif Suppresses Prolactin Expression Mol. Endocrinol., April 1, 2003; 17(4): 600 - 609. [Abstract] [Full Text] [PDF]

				T. Hirota, T. Okano, K. Kokame, H. Shirotani-Ikejima, T. Miyata, and Y. Fukada Glucose Down-regulates Per1 and Per2 mRNA Levels and Induces Circadian Gene Expression in Cultured Rat-1 Fibroblasts J. Biol. Chem., November 8, 2002; 277(46): 44244 - 44251. [Abstract] [Full Text] [PDF]

				A. Hagting, N. den Elzen, H. C. Vodermaier, I. C. Waizenegger, J.-M. Peters, and J. Pines Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1 J. Cell Biol., June 24, 2002; 157(7): 1125 - 1137. [Abstract] [Full Text] [PDF]

				Z. Wang, R. Yu, and S. Melmed Mice Lacking Pituitary Tumor Transforming Gene Show Testicular and Splenic Hypoplasia, Thymic Hyperplasia, Thrombocytopenia, Aberrant Cell Cycle Progression, and Premature Centromere Division Mol. Endocrinol., November 1, 2001; 15(11): 1870 - 1879. [Abstract] [Full Text] [PDF]

				A. P. Heaney, V. Nelson, M. Fernando, and G. Horwitz Transforming Events in Thyroid Tumorigenesis and Their Association with Follicular Lesions J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 5025 - 5032. [Abstract] [Full Text] [PDF]

				R. Yu, A. P. Heaney, W. Lu, J. Chen, and S. Melmed Pituitary Tumor Transforming Gene Causes Aneuploidy and p53-dependent and p53-independent Apoptosis J. Biol. Chem., November 17, 2000; 275(47): 36502 - 36505. [Abstract] [Full Text] [PDF]

				G. Yehia, F. Schlotter, R. Razavi, A. Alessandrini, and C. A. Molina Mitogen-activated Protein Kinase Phosphorylates and Targets Inducible cAMP Early Repressor to Ubiquitin-mediated Destruction J. Biol. Chem., September 14, 2001; 276(38): 35272 - 35279. [Abstract] [Full Text] [PDF]