PMID- 10467401 OWN - NLM STAT- MEDLINE DCOM- 19991004 LR - 20161124 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 18 IP - 32 DP - 1999 Aug 12 TI - Induction of mammary gland hyperplasia in transgenic mice over-expressing human Cdc25B. PG - 4564-76 AB - 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. FAU - Ma, Z Q AU - Ma ZQ AD - Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, TX 77030, USA. FAU - Chua, S S AU - Chua SS FAU - DeMayo, F J AU - DeMayo FJ FAU - Tsai, S Y AU - Tsai SY LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Cell Cycle Proteins) RN - EC 3.1.3.16 (Phosphoprotein Phosphatases) RN - EC 3.1.3.48 (CDC25B protein, human) RN - EC 3.1.3.48 (cdc25 Phosphatases) SB - IM MH - Animals MH - Cell Cycle Proteins/biosynthesis/genetics/*physiology MH - Cell Transformation, Neoplastic MH - Female MH - G1 Phase MH - Gene Expression MH - Genetic Vectors MH - Humans MH - Hyperplasia MH - Mammary Glands, Animal/*pathology MH - Mammary Tumor Virus, Mouse/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Phosphoprotein Phosphatases/biosynthesis/genetics/*physiology MH - Promoter Regions, Genetic MH - Rabbits MH - S Phase MH - *cdc25 Phosphatases EDAT- 1999/09/01 00:00 MHDA- 1999/09/01 00:01 CRDT- 1999/09/01 00:00 PHST- 1999/09/01 00:00 [pubmed] PHST- 1999/09/01 00:01 [medline] PHST- 1999/09/01 00:00 [entrez] AID - 10.1038/sj.onc.1202809 [doi] PST - ppublish SO - Oncogene. 1999 Aug 12;18(32):4564-76. doi: 10.1038/sj.onc.1202809.