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

• Published in: Oncogene Vol. 18; no. 32; pp. 4564 - 4576
• Main Authors: MA, Z.-Q, CHUA, S. S, DEMAYO, F. J, TSAI, S. Y
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 12.08.1999; Nature Publishing Group
• Subjects: Alveoli; Animals; Apoptosis; Biological and medical sciences; c-Myc protein; cdc25 Phosphatases; Cdc25B phosphatase; Cell Cycle Proteins - biosynthesis; Cell Cycle Proteins - genetics; Cell Cycle Proteins - physiology; Cell physiology; Cell proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cell Transformation, Neoplastic; Cyclin D1; Cyclin E; D1 protein; Epithelial cells; Female; Fundamental and applied biological sciences. Psychology; G1 Phase; Gene Expression; Genetic transformation; Genetic Vectors; Growth rate; Humans; Hyperplasia; Mammary gland; Mammary Glands, Animal - pathology; Mammary Tumor Virus, Mouse - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular and cellular biology; Myc protein; Overexpression; p53 Protein; Phosphoprotein Phosphatases - biosynthesis; Phosphoprotein Phosphatases - genetics; Phosphoprotein Phosphatases - physiology; Promoter Regions, Genetic; Rabbits; S Phase; Transgenic mice; Tumor cell lines; Tumors; Cell proliferation; Animal model; Enzyme; Induction; Phosphoprotein phosphatase; Hyperplasia; Rodentia; Phosphoric monoester hydrolases; Transgenic animal; Esterases; Gene expression; Cell transformation; Carcinogenesis; Vertebrata; Regulation(control); Mammalia; Mouse; Hydrolases; Mammary gland
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1202809

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.