Role of PELP1 in EGFR-ER Signaling Crosstalk in Ovarian Cancer Cells
Final rept. 15 Mar 2006-14 Mar 2008
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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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 PELP1MNAR is a novel NR coregulator. IHC studies using human ovarian cancer tissue arrays n123 showed that PELP1MNAR is 2 to 3 fold over expressed in 60 of ovarian tumors To examine the significance of PELP1MNAR in ovarian cancer progression, we have generated model cells that over express PELP1MNAR and ovarian cancer cells in which PELP1MNAR expression is down regulated by stable expression of PELP1MNAR-specific shRNA. Down regulation of PELP1MNAR 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. PELP1MNAR 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 PELP1MNAR signaling plays a role in ovarian cancer cell proliferation and survival, and that its expression is deregulated in ovarian carcinomas.
- Anatomy and Physiology
- Medicine and Medical Research