| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cedars-Sinai Research Institute (R.Y., S.M.), University of California Los Angeles School of Medicine, Los Angeles, California 90048; Molecular Oncology Program (W.L., J.C.), H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612; and Division of Medical Sciences (C.J.M.), University of Birmingham, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom
Address all correspondence and requests for reprints to: Shlomo Melmed, M.D., Academic Affairs, 2015, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, California 90048. E-mail: melmed{at}csmc.edu.
The mammalian securin, pituitary tumor-transforming gene (PTTG), is overexpressed in several tumors and transforms cells in vitro and in vivo. To test the hypothesis that PTTG overexpression causes aneuploidy, enhanced green fluorescent protein (EGFP)-tagged PTTG (PTTG-EGFP) was expressed in human H1299 cancer cells (with undetectable endogenous PTTG expression) and mitosis of individual live cells observed. Untransfected cells and cells expressing EGFP alone exhibited appropriate mitosis. PTTG-EGFP markedly prolonged prophase and metaphase, indicating that PTTG blocks progression of mitosis to anaphase. In cells that underwent apparently normal mitosis (35 of 65 cells), PTTG-EGFP was degraded about 1 min before anaphase onset. Cells that failed to degrade PTTG-EGFP exhibited asymmetrical cytokinesis without chromosome segregation (18 of 65 cells) or chromosome decondensation without cytokinesis (9 of 65 cells), resulting in appearance of a macronucleus. Fifty-one of 55 cells expressing a nondegradable mutant PTTG exhibited asymmetrical cytokinesis without chromosome segregation, and some (4 of 55) decondensed chromosomes, both resulting in macronuclear formation. During this abnormal cytokinesis, all chromosomes and spindles and both centrosomes moved to one daughter cell, suggesting potential chaos in the subsequent mitosis. In conclusion, failure of PTTG degradation or enhanced PTTG accumulation, as a consequence of overexpression, inhibits mitosis progression and chromosome segregation but does not directly affect cytokinesis, resulting in aneuploidy. These results demonstrate that PTTG induces aneuploidy in single, live, human cancer cells.
This article has been cited by other articles:
 |
|
 |
|
  V. Chesnokova, S. Zonis, T. Rubinek, R. Yu, A. Ben-Shlomo, K. Kovacs, K. Wawrowsky, and S. Melmed Senescence Mediates Pituitary Hypoplasia and Restrains Pituitary Tumor Growth Cancer Res., November 1, 2007; 67(21): 10564 - 10572. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wierinckx, C. Auger, P. Devauchelle, A. Reynaud, P. Chevallier, M. Jan, G. Perrin, M. Fevre-Montange, C. Rey, D. Figarella-Branger, et al. A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors Endocr. Relat. Cancer, September 1, 2007; 14(3): 887 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Rubinek, V. Chesnokova, I. Wolf, K. Wawrowsky, G. Vlotides, and S. Melmed Discordant proliferation and differentiation in pituitary tumor-transforming gene-null bone marrow stem cells Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1082 - C1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M El-Naggar, M. T Malik, A. Martin, J. P Moore, M. Proctor, T. Hamid, and S. S Kakar Development of cystic glandular hyperplasia of the endometrium in Mullerian inhibitory substance type II receptor-pituitary tumor transforming gene transgenic mice J. Endocrinol., July 1, 2007; 194(1): 179 - 191. [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]
|
|
|
|
 |
|
 G. Vlotides, M. Cruz-Soto, T. Rubinek, T. Eigler, C. J. Auernhammer, and S. Melmed Mechanisms for Growth Factor-Induced Pituitary Tumor Transforming Gene-1 Expression in Pituitary Folliculostellate TtT/GF Cells Mol. Endocrinol., December 1, 2006; 20(12): 3321 - 3335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Kim, J. A. Franklyn, K. Boelaert, M. C. Eggo, J. C. Watkinson, and C. J. McCabe Pituitary Tumor Transforming Gene (PTTG) Stimulates Thyroid Cell Proliferation via a Vascular Endothelial Growth Factor/Kinase Insert Domain Receptor/Inhibitor of DNA Binding-3 Autocrine Pathway J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4603 - 4611. [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]
|
|
|
|
 |
|
 I. Donangelo, S. Gutman, E. Horvath, K. Kovacs, K. Wawrowsky, M. Mount, and S. Melmed Pituitary Tumor Transforming Gene Overexpression Facilitates Pituitary Tumor Development Endocrinology, October 1, 2006; 147(10): 4781 - 4791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Kim, J. A. Franklyn, A. L. Stratford, K. Boelaert, J. C. Watkinson, M. C. Eggo, and C. J. McCabe Pituitary Tumor-Transforming Gene Regulates Multiple Downstream Angiogenic Genes in Thyroid Cancer J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1119 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Gillingwater, T. M. Wishart, P. E. Chen, J. E. Haley, K. Robertson, S. H.-F. MacDonald, S. Middleton, K. Wawrowski, M. J. Shipston, S. Melmed, et al. The neuroprotective WldS gene regulates expression of PTTG1 and erythroid differentiation regulator 1-like gene in mice and human cells Hum. Mol. Genet., February 15, 2006; 15(4): 625 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Chesnokova, K. Kovacs, A.-V. Castro, S. Zonis, and S. Melmed Pituitary Hypoplasia in Pttg-/- Mice Is Protective for Rb+/- Pituitary Tumorigenesis Mol. Endocrinol., September 1, 2005; 19(9): 2371 - 2379. [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]
|
|
|
|
|
|
S.-J. Tsai, S.-J. Lin, Y.-M. Cheng, H.-M. Chen, and L.-Y. C. Wing Expression and Functional Analysis of Pituitary Tumor Transforming Growth Factor-1 in Uterine Leiomyomas J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3715 - 3723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Abbud, I. Takumi, E. M Barker, S.-G. Ren, D.-Y. Chen, K. Wawrowsky, and S. Melmed Early Multipotential Pituitary Focal Hyperplasia in the {alpha}-Subunit of Glycoprotein Hormone-Driven Pituitary Tumor-Transforming Gene Transgenic Mice Mol. Endocrinol., May 1, 2005; 19(5): 1383 - 1391. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
