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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Zhang, Pumin Dong, Jie Hatcher, Rashieda J. Bian, Guangxing Wang, Tao Hilsenbeck, Susan G. Contreras, Alejandro Li, Yi Liu, Shuang |
| Description | Author Affiliation: Hatcher RJ ( Department of Molecular Physiology and Biophysics, Lester and Sue Smith Breast Center, and Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX 77030.); |
| Abstract | Pituitary tumor transforming gene 1 (Pttg1) encodes the mammalian securin, which is an inhibitor of separase (a protease required for the separation of sister chromatids in mitosis and meiosis). PTTG1 is overexpressed in a number of human cancers and has been suggested to be an oncogene. However, we found that, in Pttg1-mutant females, the mammary epithelial cells showed increased proliferation and precocious branching morphogenesis. In accord with these phenotypic changes, progesterone receptor, cyclin D1, and Mmp2 were up-regulated whereas p21 (Cdkn1a) was down-regulated. These molecular changes provide explanation for the observed developmental defects, and suggest that Pttg1 is a tumor suppressor. Indeed, mice lacking Pttg1 developed spontaneous mammary tumors. Furthermore, in human breast tumors, PTTG1 protein levels were down-regulated and the reduction was significantly correlated with the tumor grade. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 3 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Mammary Glands, Animal Physiology Mammary Neoplasms, Animal Metabolism Securin Animals Apoptosis Breast Neoplasms Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic Genetics Chromatids Chemistry Cyclin-Dependent Kinase Inhibitor P21 Epithelial Cells Cytology Gene Expression Profiling Growth & Development Mice Mice, Inbred C57BL Mice, Knockout Neoplasm Proteins Time Factors Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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