Abstract 991: Regulation of glucose metabolism by HIF in pancreatic cancer

Abstract

Abstract Pancreatic cancer is the fourth leading cause of cancer related deaths with a five-year survival rate of 5.5%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. Like other cancers, pancreatic cancer displays alterations in cellular metabolism, which holds significant promise for better management/cure of the disease. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. Several oncogenes and tumor suppressors have been implicated in altering tumor cell metabolism in order to facilitate tumor growth and metastasis. The objective of this study was to characterize the role of hypoxia inducible factors (HIF) in glucose metabolism in pancreatic cancer cell lines under normoxic and hypoxic conditions. We screened a panel of pancreatic cancer cell lines for glucose uptake under normoxic and hypoxic conditions. Although the effect of hypoxia on glucose uptake was variable in different pancreatic cancer cell lines, it correlated well with the expression levels of HIF-1alpha and HIF-2alpha. Furthermore, dual knockdown of HIF-1alpha and HIF-2alpha had similar negative effect on growth rate under hypoxic conditions, as did the treatment with glycolysis inhibitor 3-BrPA. These studies suggest that HIF factors regulate growth in pancreatic cancer by regulating glycolysis. Hence, combining strategies to target metabolism along with the strategies to target signal transduction might synergistically aid in diminishing cancer cell growth and invasiveness. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 991. doi:10.1158/1538-7445.AM2011-991