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

Oncogene volume 18, pages 4564–4576 (1999)Cite this article

Abstract

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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Acknowledgements

We would like to thank Drs Daniel Medina, Jeffery Gimble, Mong-Hong Lee, Ming-Jer Tsai and Fred A Pereira for their valuable discussions. We are also grateful to Drs David Beach and Brigid Hogan for their generous gift of the human Cdc25B and MMTV-KCR plasmids respectively. Last but not least, we would also like to extend our acknowledgements to Lei Gong, LouAnn Hadsell and John Stockton for their excellent technical support. This work was supported by a grant of DAMD 1794J4400 to SYT.

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  1. Zhi-Qing Ma and Steven S Chua: Z-Q Ma and SS Chua contributed equally to this work

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  1. Department of Cell Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, Texas, USA

    Zhi-Qing Ma, Steven S Chua, Francesco J DeMayo & Sophia Y Tsai

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Ma, ZQ., Chua, S., DeMayo, F. et al. Induction of mammary gland hyperplasia in transgenic mice over-expressing human Cdc25B. Oncogene 18, 4564–4576 (1999). https://doi.org/10.1038/sj.onc.1202809

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