A Role for MEK-Interacting Protein 1 in Hormone Responsiveness of ER Positive Breast Cancer Cells
Abstract
We have identified a novel role for the small scaffold protein MP1 in the survival of ER-positive breast cancer cell lines. Blocking MP1 expression using siRNA leads to apoptotic cell death in ER-positive MCF-7, LCC9 and T47D cells, but not in ER-negative MDA-MB-231, SKBr3 and BT-549 cell, or in non-tumorigenic 184B5 cells. Inhibition of MP1 expression in MCF-7 cells resulted in decreased ER expression and activity, and decreased AKT phosphorylation. We therefore hypothesize that a loss of pro-survival signaling from one or both of these molecules may be responsible for the cell death observed upon MP1 knockdown. In addition, we have obtained preliminary evidence suggesting that inhibiting MP1 expression in ER-positive cells leads to decreased expression of several integrins, which may also contribute to the cell detachment and/or death observed. The current targeted therapies for ER-positive tumors (antiestrogens and aromatase inhibitors) induce a cell cycle arrest, but not rapid cell death. Our results suggest that MP1 or one of the pro-survival pathways that it regulates could provide novel targets for the treatment of ER-positive breast tumor. If such treatments result in cell death, they may provide advantages over current therapies such as decreased treatment time.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2010
- Accession Number
- ADA540806
Entities
People
- Susan E. Conrad
Organizations
- Michigan State University