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Publication : Induction of mammary gland hyperplasia in transgenic mice over-expressing human Cdc25B.

First Author  Ma ZQ Year  1999
Journal  Oncogene Volume  18
Issue  32 Pages  4564-76
PubMed ID  10467401 Mgi Jnum  J:174264
Mgi Id  MGI:5052260 Doi  10.1038/sj.onc.1202809
Citation  Ma ZQ, et al. (1999) Induction of mammary gland hyperplasia in transgenic mice over-expressing human Cdc25B. Oncogene 18(32):4564-76
abstractText  Cdc25 A and B are dual-specificity phosphatases which have been implicated in neoplastic transformation. Although Cdc25A and Cdc25B have been found to be over-expressed in many cancer cell lines and primary tumors, the physiological roles of Cdc25A and B in vivo are largely undefined. To investigate the roles of these proteins in the oncogenic transformation of the mammary gland we used the mouse mammary tumor virus (MMTV) promoter to target over-expression of the Cdc25B transgene in the mammary glands of transgenic mouse lines. Here we report that the over-expression of Cdc25B enhances the proliferation of mammary epithelial cells resulting in the formation of precocious alveolar hyperplasia. At the molecular level, marked increases in cyclin D1 protein have been found in transgenic mammary epithelial cells. The accelerated growth rate of the mammary epithelial cells could also be attributed to the increased levels of cyclin E/cdk2 activity. In addition, a pronounced decrease in apoptosis was also observed during the involution of mammary gland. The reduction of apoptosis during involution correlated well with the reduced expression of c-myc and p53, both of which have been implicated in apoptosis. Taken together, our results clearly indicate that the deregulated expression of Cdc25B generates mammary gland hyperplasia.
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