Ras, p16 Expression Levels and Cancer Cell Metabolism

The Warburg effect is an alteration of metabolism in cancer cells marked by aerobic glycolysis and lactic acid fermentation even in the presence of normal oxygen levels. Oncogenes involved in cellular proliferation pathways have also been found to play a role in this alteration of cellular metabolism. We aim to engineer the MCF10A cell line as a model cell line to investigate the combined effects of oncogenic RasG12V and tumor suppressor protein p16 on cellular metabolism. Expression constructs for ras and p16 are inserted into MCF10A cells (null for p16) via viral vectors, and expression is controlled by varying translation initiation strengths and inducible systems (dihydrofolate reductase and estrogen receptor tags). Cellular metabolism changes are observed via fluorometric assays that measure lactate concentrations in the cell culture media. A greater understanding of ras and p16 effects on cancer cell metabolism may reveal mechanisms of cancer development and areas for potential therapeutic targets.