Abstract 2241: MDM2 silencing promotes tumor-initiating cells in osteosarcoma and breast cancer

Abstract

Abstract Chemotherapy has made remarkable strides in the past century to alleviate tumor burden across most cancer types, yet it remains ineffective at achieving complete tumor remission. To improve chemotherapy efficacy and patient survival, novel drugs will require a greater mechanistic understanding of tumor initiating cell (TIC) regulatory pathways. Intratumoral heterogeneity is a major obstacle for conventional targeted treatment modalities, which select for aggressive phenotypes with acquired drug resistance and TIC enrichment. Here we focus on elucidating the role of Mdm2 in mediating TIC levels in osteosarcoma (MG-63, Saos2) and breast cancer (MDA 231, MDA 468, and BT474) cell lines. We demonstrate Mdm2 silencing by ShRNA results in increased levels of Nanog, Oct4a, and Sox2, and diminished expression of ERα and ERβ by western blot. We observed an increase in the immunophenotypic expression of CD133 in ShMdm2 osteosarcoma and breast cancer cell lines by flow cytometry. Our data provides the first evidence that loss of Mdm2 results in increased TIC population. Further analysis will examine the affects of TIC using small molecular inhibitors to Mdm2. This insight will contribute to the molecular foundations defining the role of Mdm2 in TIC and will determine if targeting Mdm2 therapeutically is a prognostic indicator for recurrence. Citation Format: David J. Olivos, Lindsey D. Mayo. MDM2 silencing promotes tumor-initiating cells in osteosarcoma and breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2241. doi:10.1158/1538-7445.AM2015-2241