A Role for MEK-Interacting Protein 1 In Hormone Responsiveness of ER Positive Breast Cancer Cells
Final rept. 1 Jul 2007-30 Sep 2011
MICHIGAN STATE UNIV EAST LANSING
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MEK Partner 1 MP1 or MAPKSP1 is a scaffold protein that functions in multiple signaling pathways that play important roles in breast cancer, and is expressed in both ER-positive and negative breast cancer cell lines. We investigated MP1 function in these cells using RNA interference to silence the MP1 gene. MP1 gene silencing resulted in detachment and apoptosis of ER-positive breast cancer cell lines, but not ER-negative breast cancer or non-tumorigenic mammary epithelial cell lines. The apoptosis observed in ER-positive cells was correlated with decreased AKT activity, and expression of a constitutively active form of AKT1 partially rescued the cell death phenotype. Together, these results suggest that MP1 is required for pro-survival signaling from the PI3KAKT pathway in ER-positive breast cancer cells, and that it may provide a novel target for the treatment of ER-positive breast tumors.
- Medicine and Medical Research