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

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 physio logical roles of Cdc25A and B in vivo are largely undefined. To investigate the roles of these proteins in the ontogenic 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 mou se Lines. Here we report that the over-expression of Cdc25B enhances the pr oliferation of mammary epithelial cells resulting in the formation of preco cious alveolar hyperplasia. At the molecular level, marked increases in cyc lin D1 protein have been found in transgenic mammary epithelial cells. The accelerated growth rate of the mammary epithelial cells could also be attri buted to the increased levels of cyclin E/cdk2 activity, In addition, a pro nounced decrease in apoptosis was also observed during the involution of ma mmary gland, The reduction of apoptosis during involution correlated well w ith the reduced expression of c-myc and p53, both of which have been implic ated in apoptosis. Taken together, our results clearly indicate that the de regulated expression of Cdc25B generates mammary gland hyperplasia.