Abstract 207: Regulation of mitochondrial biogenesis in primary human clear cell renal cell carcinoma cells

Abstract

Abstract Clear cell renal cell carcinoma, ccRCC, is the most prevalent type of kidney cancer. In over 90% of ccRCCs the tumor suppressor protein von Hippel Lindau is inactivated, leading to a pseudohypoxic phenotype with vast effects on angiogenesis as well as energy metabolism. In accordance with the Warburg effect, aerobic glycolysis increases, while mitochondrial oxidative phosphorylation is decreased. We have previously published data showing that also the number and activity of mitochondria is strikingly reduced in primary human ccRCC cells compared to normal kidney epithelial cells. This was not seen in any of the established RCC cell lines included in the study. We are now continuing these studies by investigating the regulation of mitochondrial biogenesis in primary human ccRCC cells, and how the number and activity of mitochondria influences the tumorigenic properties of these cells. RNA has been isolated from ccRCC tissue areas identified as mitochondria high or low. The expression profile in these samples will be analyzed by RNA sequencing. Human primary ccRCC cells obtained from patient nephrectomies are kept in culture and the regulation of mitochondrial biogenesis in these cells is investigated. How the mitochondrial content affects tumorigenic properties such as proliferation, migration and resistance to apoptosis is also investigated. Preliminary data indicate that primary ccRCC cells have an absent or severly limited capability to increase the number of mitochondria on metabolic demand, and that the regulation of mitogenesis is defective. These results point towards a malfunctioning energy sensing and mitochondrial biogenesis in ccRCC cells that might be part of the explanation to the very low mitochondrial content in these cells. Citation Format: Helén Å. Nilsson, Martin E. Johansson. Regulation of mitochondrial biogenesis in primary human clear cell renal cell carcinoma cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 207.