A Role for MEK-Interacting Protein 1 in Hormone Responsiveness of ER Positive Breast Cancer Cells
Abstract
Our results have revealed a critical and previously unreported role for the small scaffold protein MP1 in the survival of ER-positive, but not ER-negative 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 cells. Overexpression of MP1 may also be toxic to ER-positive cells, since MCF-7 derivatives expressing ectopic MP1 are unstable and rapidly lose expression of the transfected MP1 gene upon passage. The mechanism by which MP1 affects survival of ER-positive breast cancer cells is not known, but may be the result of alterations in ER levels and/or functions. In support of this hypothesis, MP1 knockdown leads to decreased ER levels, and MP1 overexpression to increased ER levels. Together, out data strongly suggest that MP1 could provide a novel target for the treatment of ER-positive breast tumors. Future experiments will investigate the mechanism(s) by which MP1 regulates survival of ER-positive breast cancer cells, and those by which it regulates ER levels and function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2009
- Accession Number
- ADA514031
Entities
People
- Susan E. Conrad
Organizations
- Michigan State University