Mechanisms for Controlling Breast Cancer Growth and Skeletal Metastasis
Annual rept. 15 May 1999-14 May 2000
TEXAS UNIV HEALTH SCIENCE CENTER AT SANANTONIO
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Bone morphogenetic protein-2 BMP-2, a potential growth factor for osteogenesis, inhibited estrogen-responsive growth of MCF-7 breast cancer cells. The mechanism involved inhibition of estrogen-induced mitogen activated protein kinase MAPK activity by BMP-2. BMP-2 also inhibited cell cycle progression in MCF-7 cells by increasing the level of a cyclin dependent kinase CDK inhibitor CKI, namely, p2l. This in turn resulted in inhibition of CDK activities which inhibited phosphorylation of retinobastoma protein pBb. pBb phosphorylation is tightly linked with its activity in cell cycle progression. Thus by inhibiting pRb phosphorylation BMP-2 arrested the cell cycle at the Gl phase and thus inhibited uncontrolled proliferation of these cells. In order to extend this finding in a clinical background we are now establising animal models of human breast cancer cell growth in which we are going to express BMP-2 under a tetracyclin regulatable promoter in the breast cancer cells. We have generated cell lines using these expression plasmids and have started to characterize them. We will also analyze breast cancer tissue samples for the expression of BMP-2 and its receptors. Once the analysis is complete, we will categorize the cancer samples in terms of their growth and metastasis property.
- Anatomy and Physiology
- Medicine and Medical Research