Counteraction of the Antiapoptotic Protein Survivin by Diverting Expression to its Proapoptotic Splice Variant Survivin-2B. Annual Summary January 1, 2009-December 31, 2009

摘要

Abnormal glucose metabolism is associated with increased cancer risk, which is independent of body mass index for several types of cancer, with a stronger association for women than for men and for fatal cancer. The hypothesis we investigated is the following: In a proliferation-inhibited state, survivin-2B will be shifted from a rare into a major variant, and survivin will be shifted from a major into a rare variant. In order to test this hypothesis we used glucose deprivation as a model to inhibit proliferation capacity and induce apoptosis, and analyzed endogenous survivin and survivin-2B expression in a proliferation-inhibited (low glucose) verses proliferation-promoted (high glucose) state brought about by varying extracellular glucose in media in which human breast cancer cells were cultured. Further, our experiments are trying to determine the extent of tumor cell dependence on glucose for survival and proliferation, and the relationship with survivin gene regulation. To our knowledge this is the first finding to provide evidence that the survivin gene (survivin and survivin-2B) is down-regulated by low glucose. This report highlights our findings arising from my DoD Breast Cancer Pre-Doctoral Traineeship Award project.