Roles of Steroid Receptor Coactivators in Breast Cancer
Final rept. 1 Aug 1999-31 Dec 2003
INDIANA UNIV INDIANAPOLIS
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The purpose of this study is to determine the roles of steroid receptor coactivators in breast cancer. The scope of the research is to assess the expression and functions of SRC-1 family members SRC-1, GRIP1, and AIB1 in normal mammary gland and in breast tumors. We found that the expression of SRC-1 family members was regulated by ovarian hormones during mammary gland development. We also found that AIB1 protein was overexpressed in human breast cancer specimens, as compared to adjacent normal breast tissue. In addition, functions of these coactivators have been studies during the funding period. We have constructed adenovirus expressing these three coactivtors. In addition, increased expression of AIB1 in human breast cancer cells stimulated the S phase entry during cell cycle progression, indicating the involvement of AIB1 in cell cycle control and cell growth of human breast cancer cells. Furthermore, overexpresson of AIB1 dramatically increased the phosphorylation of Akt and Akt kinase activity in human breast cancer cells. AIB1 was also able to stimulate c-Src signaling. These studies provide important insights how AIB1 works in human breast cancer cells to promote breast cancer progression.
- Medicine and Medical Research