Abstract A21: ACC1 is required for prostate cancer initiation, but not progression?

The majority of cancers undergo metabolic alterations during initiation and progression of disease. Increased de novo lipogenesis is recognized as metabolic mark of cancer cells. The enzymes responsible for de novo fatty acid synthesis are often overexpressed in cancer, indicating that these enzymes are potential and promising targets for novel therapies. Acetyl CoA Carboxylase 1 (ACC1) is a cytosolic enzyme which catalyzes the rate limiting step of de novo fatty acid synthesis through the ATP and biotin-dependent carboxylation of acetyl-CoA to malonyl-CoA. In doing so, it regulates both fatty acid and acetate metabolism. Both pharmacological inhibition and siRNA knockdown of ACC1 have been demonstrated to deny prostate cancer cells of necessary amounts of fatty acids needs to proliferate, resulting in selective toxicity. Although previous research indicates ACC1 and the entire process of fatty acid metabolism to be promising avenues for novel therapy development, much remains to be understood. To address this, we have generated mice with prostate-specific deletion of exon 22 of the Acetyl CoA Carboxylase 1 (ACCL/L) gene by breeding with Probasin-Cre mice. Loss of ACC1 activity does not affect prostate development as survival, prostate weight, histology, and breeding were similar between ACCL/L; Cre+ and ACCL/L Cre- mice. By breeding ACC+/L mice with the established Pten knockout model of prostate cancer (PtenL/L; Cre+), we have found that homozygous inactivation of ACC1 (ACC...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Metabolic Pathways: Poster Presentations - Proffered Abstracts Source Type: research