Abstract 5670: Phospho-PEA-15 sensitizes ovarian cancer cells to paclitaxel by impairing the microtubule-destabilizing effect of SCLIP

Paclitaxel is a standard chemotherapeutic agent for ovarian cancer. Resistance of ovarian cancer cells to the drug has been a major obstacle in clinical practice. Thus, alternative approaches are needed to conquer the resistance. PEA-15 (phosphoprotein enriched in astrocytes-15 kDa) regulates cell proliferation and apoptosis. It is phosphorylated at S104 and S116 by Akt, PKC and CaMKII. PEA-159s functions are phosphorylation dependent. Although PEA-15 is known to mediate chemoresistance in breast cancer, the effect of PEA-15 phosphorylation status on chemosensitivity remains unknown. We hypothesized that phospho-PEA-15 (pPEA-15) enhances sensitivity of ovarian cancer cells to paclitaxel. To test our hypothesis, we silenced PEA-15 expression in HEY and OVTOKO cells using siRNA and observed a 14% reduction in apoptosis after paclitaxel exposure. To further determine if PEA-15 phosphorylation contributes to chemosensitivity, we generated SKOV3.ip1-vector (control), SKOV3.ip1-AA (AA, phosphoinhibitory at S104 and S116) and SKOV3.ip1-DD (DD, phosphomimetic at S104 and S116) stable ovarian cancer cells. Compared to the control, DD cells showed a 15% reduction in cell viability (P Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5670. doi:1538-7445.AM2012-5670