Abstract A22: Cell growth regulation of gain-of-function mutant p53 via miRNAs on metabolic inhibition

Abstract

Abstract There is growing evidence that tumor cells depend on unique metabolism for their continued growth and survival, and that cancer cells are peculiarly addicted to the rapacious uptake of glucose and glutamine. Due to the gain-of-function, mutant p53 protein contributes to tumor metastasis and shortening the latency of tumor progression, and thereby activated K-ras/mutant p53 mouse is preferentially used as lung adenocarcinoma preclinical model. Epigenetic regulation through histone modification or miRNA also plays a pivotal role on gene regulation, as regarded as global epigenetic markers, especially in tumor related genes. Hence, chemical approaches targeting histone-modifying enzymes have emerged onto the main stage of anticancer drug discovery. Here, we have investigated the involvement of miRNAs in cell growth regulation upon the treatment of metabolic inhibitors. We have generated different genotypes of mouse tumor cells derived from activated mutant p53 and/or K-ras mutant mice. We have tested whether inhibitors regulating metabolism induce adverse effect on cell growth and changes of miRNA expression through microarray analysis, with the hint of enormous demands for nutrients in fast growing tumor cells. We then analyzed affected genes and miRNAs via quantitative RT-PCR to confirm the involvement of miRNAs on cell growth when tumor metabolic environment were damaged. Citation Format: Se-Young Jo, Hae-Min Moon, ChuHee Lee, Se Jin Jang, Young-Ah Suh. Cell growth regulation of gain-of-function mutant p53 via miRNAs on metabolic inhibition. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A22.