Glycolytic Phenotype and Growth Properties Preserved in a HIF-1β Deficient Tumor Cell Line

• 作 者: MonikaGolinska;JohnGriffiths;
• 机 构: Cambridge Research Institute Li Ka Shing Centre UK
• 出 处: BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
• 发表日期: 2009年期

　　Cells respond to low oxygen levels by activating a transcription factor called HIF-1, which then upregulates the expression of a variety of genes including those controlling glucose metabolism, angiogenesis, cell growth and differentiation.HIF-1 expression is often upregulated in cancer, and it is also activated as tumors are often hypoxic; both effects are thought to contribute to the altered metabolism of tumour cells.Healthy cells metabolise glucose to pyruvate in the presence of oxygen and to lactate in its absence.Cancer cells in contrast always perform aerobic glycolysis and produce lactate.This phenomenon, called the Warburg effect, has been studied by our group in a HIF-1β deficient hepatoma mouse model (mutant), in which active HIF-1 cannot be formed as the oxygen-sensitive HIF-1α molecule cannot bind to its HIF-1β partner.Mutant cells unable to active HIF-1 should not be able to upregulate glycolysis, and indeed we have found that their glycolytic enzymes are downregulated.