Abstract 1349: Chemosensitization of breast cancer cell lines by Ell3

Ell3 is a RNA polymerase II transcription elongation factor that is enriched in testis. The C-terminal domain of Ell3 shows strong similarities to that of Ell (eleven-nineteen lysine-rich leukemia gene), which acts as a negative regulator of p53. Recent studies in our laboratory showed that Ell3 induces the differentiation of mouse embryonic stem cells by protecting differentiating cells from apoptosis by the promotion of p53 degradation. In this study, we evaluated the function of Ell3 in breast cancer cell lines. Contrary to our expectation, ectopic expression of Ell3 in MCF7 induces CDDP (cisplatin) susceptibility by enhancing p53 dependent apoptosis. CDDP treatments leads to the accumulation of p53 protein in the Ell3 overexpressing MCF7. We confirmed that Ell3 inhibits proteosomal degradation of p53 upon cisplatin treatment in MCF7. Ell3 also confer chemosensitivity to MCF7 to DNA damaging agent, camptothecin. The treatment of camptothecin to Ell3 overexpressing MCF7 results in the accumulation of cells at G2/M phase of cell cycle by the increases of p53 protein. Consistent with these results, Ell3 downregulates the expression of MDM2, which binds p53 and marks it for degradation using the proteasome. The underlying mechanism of Ell3 to regulate MDM2 expression is under investigation. Citation Format: Hee-Jin Ahn, Sun-Hee Heo, Gwangil Kim, Kyung-Soon Park. Chemosensitization of breast cancer cell lines by Ell3 . [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1349. doi:10.1158/1538-7445.AM2014-1349