Role of PELP1 in EGFR-ER Signaling Crosstalk in Ovarian Cancer Cells
Abstract
Emerging evidence suggests that nuclear receptor (NR) coregulators have potential to act as master genes and their deregulation can promote oncogenesis. Proline-, glutamic acid-, and leucine-rich protein-1 (PELP1/MNAR) is a novel NR coregulator. IHC studies using human ovarian cancer tissue arrays (n=123) showed that PELP1/MNAR is 2 to 3 fold over expressed in 60% of ovarian tumors To examine the significance of PELP1/MNAR in ovarian cancer progression, we have generated model cells that over express PELP1/MNAR and ovarian cancer cells in which PELP1/MNAR expression is down regulated by stable expression of PELP1/MNAR-specific shRNA. Down regulation of PELP1/MNAR in cancerous ovarian model cells (OVCAR3) resulted in reduced proliferation, affected the magnitude of c-Src and AKT signaling and reduced tumorigenic potential of ovarian cancer cells in a nude mouse model. PELP1/MNAR over expression in nontumorigenic immortalized surface epithelial cells (IOSE cells) promoted constitutive activation of c-Src and AKT signaling pathways and promoted anchorage independent growth. PELP knock down affected EGF mediated activation of cytoskeletal reorganization and increased sensitivity of chemotherapy drugs. Collectively these results suggest that PELP1/MNAR signaling plays a role in ovarian cancer cell proliferation and survival, and that its expression is deregulated in ovarian carcinomas.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2008
- Accession Number
- ADA509750
Entities
People
- Ratna K. Vadlamudl
Organizations
- University of Texas Health Science Center at San Antonio