Role of PELP1 in EGFR-ER Signaling Crosstalk in Ovarian Cancer Cells
Annual rept. 15 Mar 2006-14 Mar 2007
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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Proline-, glutamic acid-, and leucine-rich protein PELP1, is a novel nuclear receptor NR coregulator. PELP1MNAR serves as a scaffolding protein, participates in genomic and nongenomic functions of NRs and its expression is shown to be deregulated in hormonally responsive cancers. However little is known about PELP1 role in ovarian cancer progression. To examine the significance of PELP1 in ovarian cancer progression, we have generated model cells that overexpress PELP1 IOSE-PELP1 and BG-1 PELP1 and ovarian cancer cells in which PELP1 expression is down regulated by stable expression of PELP1 specific shRNA OVCAR3-PELP1-shRNA and SKOV3-shRNA. PELP1 overexpression in IOSE and BG1 model cells resulted in alterations in cell morphology with increased F-Actin containing structures including ruffles and filopodia. Analysis of cellular signalling pathways using phospho-specific antibodies revealed constitutive activation of c-Src kinase and increased phosphorylation of estrogen receptor. The expression of PELP1-shRNA in OVCAR3 cells dramatically decreased endogenous PELP1 expression and showed defects in cytoskeletal reorganization upon growth factor stimulation and exhibited low proliferation rate in invitro cell culture assays and invivo nude mice assays. Collectively these results suggest that PELP1 play a role in ovarian cancer cell proliferation and migration, and its expression is deregulated in ovarian carcinomas.
- Medicine and Medical Research