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Molecular Endocrinology 11 (4): 433-441
Copyright © 1997 by The Endocrine Society

Isolation and Characterization of a Pituitary Tumor-Transforming Gene (PTTG)

Lin Pei and Shlomo Melmed1

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

Pathogenesis of tumor formation in the anterior pituitary has been intensively studied, but the common mechanism involved in pituitary cell transformation and tumorigenesis remains elusive. In this study, we used mRNA differential display PCR to identify mRNAs that are differentially expressed in rat pituitary tumor cells compared with normal pituitary tissue. An mRNA exclusively expressed in pituitary tumor but not in normal pituitary was characterized. Using this pituitary tumor-specific PCR product as a probe to screen a cDNA library constructed from rat pituitary tumor GH4 cells, a cDNA of 974 bp was isolated. This cDNA encodes a novel protein of 199 amino acids, which contains no well characterized functional motifs. The mRNA of this cDNA is detected in normal adult testis and in embryonic liver, where the transcript is about 300 bp shorter and expressed at a much lower level than that detected from pituitary tumor cells. Overexpression of this protein in mouse 3T3 fibroblasts shows that it inhibits cell proliferation and induces cell transformation in vitro. Injection of transfected 3T3 cells into athymic nude mice resulted in tumor formation within 3 weeks in all animals. These results indicate that pituitary tumor cells express a unique and potent transforming gene (PTTG), which may play a role in pituitary tumorigenesis.




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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]


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Mol. Biol. CellHome page
M. L. Whitfield, G. Sherlock, A. J. Saldanha, J. I. Murray, C. A. Ball, K. E. Alexander, J. C. Matese, C. M. Perou, M. M. Hurt, P. O. Brown, et al.
Identification of Genes Periodically Expressed in the Human Cell Cycle and Their Expression in Tumors
Mol. Biol. Cell, June 1, 2002; 13(6): 1977 - 2000.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
J. A. Fagin
Minireview: Branded from the Start--Distinct Oncogenic Initiating Events May Determine Tumor Fate in the Thyroid
Mol. Endocrinol., May 1, 2002; 16(5): 903 - 911.
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J. Clin. Endocrinol. Metab.Home page
X. Zhang, H. Sun, D. C. Danila, S. R. Johnson, Y. Zhou, B. Swearingen, and A. Klibanski
Loss of Expression of GADD45{gamma}, a Growth Inhibitory Gene, in Human Pituitary Adenomas: Implications for Tumorigenesis
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1262 - 1267.
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Endocr. Rev.Home page
N. Ben-Jonathan and R. Hnasko
Dopamine as a Prolactin (PRL) Inhibitor
Endocr. Rev., December 1, 2001; 22(6): 724 - 763.
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J. Histochem. Cytochem.Home page
S. S. Kakar, L. Chen, R. Puri, S. E. Flynn, and L. Jennes
Characterization of a Polyclonal Antibody to Human Pituitary Tumor Transforming Gene 1 (PTTG1) Protein
J. Histochem. Cytochem., December 1, 2001; 49(12): 1537 - 1546.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
M. L. Brinkmeier, J. H. Stahl, D. F. Gordon, B. D. Ross, V. D. Sarapura, J. M. Dowding, S. K. Kendall, R. V. Lloyd, E. C. Ridgway, and S. A. Camper
Thyroid Hormone-Responsive Pituitary Hyperplasia Independent of Somatostatin Receptor 2
Mol. Endocrinol., December 1, 2001; 15(12): 2129 - 2136.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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Nucleic Acids ResHome page
F. Romero, M.-C. Multon, F. Ramos-Morales, A. Dominguez, J. A. Bernal, J. A. Pintor-Toro, and M. Tortolero
Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase
Nucleic Acids Res., March 15, 2001; 29(6): 1300 - 1307.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
H. Ishikawa, A. P. Heaney, R. Yu, G. A. Horwitz, and S. Melmed
Human Pituitary Tumor-Transforming Gene Induces Angiogenesis
J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 867 - 874.
[Abstract] [Full Text]


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Clin. Cancer Res.Home page
R. N. Clayton, M. Pfeifer, A. B. Atkinson, P. Belchetz, J. A. H. Wass, E. Kyrodimou, M. Vanderpump, D. Simpson, J. Bicknell, and W. E. Farrell
Different Patterns of Allelic Loss (Loss of Heterozygosity) in Recurrent Human Pituitary Tumors Provide Evidence for Multiclonal Origins
Clin. Cancer Res., October 1, 2000; 6(10): 3973 - 3982.
[Abstract] [Full Text]


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Genes Dev.Home page
O. Leismann, A. Herzig, S. Heidmann, and C. F. Lehner
Degradation of Drosophila PIM regulates sister chromatid separation during mitosis
Genes & Dev., September 1, 2000; 14(17): 2192 - 2205.
[Abstract] [Full Text]


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Mol. Endocrinol.Home page
R. Yu, S.-G. Ren, G. A. Horwitz, Z. Wang, and S. Melmed
Pituitary Tumor Transforming Gene (PTTG) Regulates Placental JEG-3 Cell Division and Survival: Evidence from Live Cell Imaging
Mol. Endocrinol., August 1, 2000; 14(8): 1137 - 1146.
[Abstract] [Full Text]


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ScienceHome page
K. Nasmyth, J. Peters, and F. Uhlmann
Splitting the Chromosome: Cutting the Ties That Bind Sister Chromatids
Science, May 26, 2000; 288(5470): 1379 - 1384.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
Z. Wang and S. Melmed
Pituitary Tumor Transforming Gene (PTTG) Transforming and Transactivation Activity
J. Biol. Chem., March 10, 2000; 275(11): 7459 - 7461.
[Abstract] [Full Text] [PDF]


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EndocrinologyHome page
Z. Wang and S. Melmed
Characterization of the Murine Pituitary Tumor Transforming Gene (PTTG) and Its Promoter
Endocrinology, February 1, 2000; 141(2): 763 - 771.
[Abstract] [Full Text] [PDF]


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ScienceHome page
H. Zou, T. J. McGarry, T. Bernal, and M. W. Kirschner
Identification of a Vertebrate Sister-Chromatid Separation Inhibitor Involved in Transformation and Tumorigenesis
Science, July 16, 1999; 285(5426): 418 - 422.
[Abstract] [Full Text]


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Endocr. Rev.Home page
P. L. M. Dahia and A. B. Grossman
The Molecular Pathogenesis of Corticotroph Tumors
Endocr. Rev., April 1, 1999; 20(2): 136 - 155.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
X. Zhang, G. A. Horwitz, A. P. Heaney, M. Nakashima, T. R. Prezant, M. D. Bronstein, and S. Melmed
Pituitary Tumor Transforming Gene (PTTG) Expression in Pituitary Adenomas
J. Clin. Endocrinol. Metab., February 1, 1999; 84(2): 761 - 767.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
L. Pei
Pituitary Tumor-transforming Gene Protein Associates with Ribosomal Protein S10 and a Novel Human Homologue of DnaJ in Testicular Cells
J. Biol. Chem., January 29, 1999; 274(5): 3151 - 3158.
[Abstract] [Full Text] [PDF]


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Mol. Endocrinol.Home page
X. Zhang, G. A. Horwitz, T. R. Prezant, A. Valentini, M. Nakashima, M. D. Bronstein, and S. Melmed
Structure, Expression, and Function of Human Pituitary Tumor-Transforming Gene (PTTG)
Mol. Endocrinol., January 1, 1999; 13(1): 156 - 166.
[Abstract] [Full Text]


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Endocr. Rev.Home page
S. L. Asa and S. Ezzat
The Cytogenesis and Pathogenesis of Pituitary Adenomas
Endocr. Rev., December 1, 1998; 19(6): 798 - 827.
[Abstract] [Full Text]


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J. Biol. Chem.Home page
L. Pei
Genomic Organization and Identification of an Enhancer Element Containing Binding Sites for Multiple Proteins in Rat Pituitary Tumor-transforming Gene
J. Biol. Chem., February 27, 1998; 273(9): 5219 - 5225.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
L. Pei
Activation of Mitogen-activated Protein Kinase Cascade Regulates Pituitary Tumor-transforming Gene Transactivation Function
J. Biol. Chem., September 29, 2000; 275(40): 31191 - 31198.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
L. Pei
Identification of c-myc as a Down-stream Target for Pituitary Tumor-transforming Gene
J. Biol. Chem., March 9, 2001; 276(11): 8484 - 8491.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
W. Chien and L. Pei
A Novel Binding Factor Facilitates Nuclear Translocation and Transcriptional Activation Function of the Pituitary Tumor-transforming Gene Product
J. Biol. Chem., June 16, 2000; 275(25): 19422 - 19427.
[Abstract] [Full Text] [PDF]




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