The Bmi-1 polycomb group gene in skin cancer: Regulation of function by (-)-epigallocatechin-3-gallate

Abstract

The results of our studies support several conclusions. First, the Bmi-1 PcG gene product is expressed at high levels in skin tumors and in cultured squamous cell carcinoma cells, indicating that Bmi-1 may play a role in enhancing skin tumor cell survival. Second, Bmi-1 is present in a wide range of cells in tumors. Thus, although Bmi-1 has been thought to be restricted to maintaining stem cell survival, the ubiquitous distribution of Bmi-1 in skin tumor cells suggests a broader role in skin cancer. Third, our studies suggest that Bmi-1 may be a downstream mediator of EGCG action. This idea is supported by the finding that treatment with EGCG reduces Bmi-1 level and increases Bmi-1 phosphorylation (unpublished). Increased Bmi-1 phosphorylation is associated with reduced Bmi-1 activity. We therefore propose that EGCG may reduce cancer cell survival by altering epigenetic control of gene expression, via its ability to reduce Bmi-1 function. Fourth, our studies suggest that Bmi-1 controls the balance between skin cancer survival and death by modulating the balance between cell apoptosis and proliferation (summarized in Fig. 1), and that this is achieved via regulation of cyclin-dependent kinase function and control of the apoptosis cascades. © 2008 International Life Sciences Institute.