| A defining characteristic of solid tumors is the capacity to divide and spread under conditions of nutrient deprivation and limited oxygen availability. These micro-environmental stresses arise from structural abnormalities in tumor vessels that lead to aberrant microcirculation. Hypoxia acts as a physiological "selection pressure" in the progression of cancer by activating pathways and enhancing the expression of specific genes in tumor cells which eventually diminish their apoptotic potential. Ultimately, hypoxic microenvironment functions as a "stress factor", selecting cells with the ability to survive and divide under anoxic conditions. The members of the PIM family of cytoplasmic serine threonine kinases are true oncogenes that function as survival factors in response to many stresses. We have previously reported that PIM1 is upregulated during cytotoxic drug-induced stress and improves survival of PCa cell lines.;In this study we hypothesized that the activation of HIF-1alpha and STAT3 in hypoxia up-regulates the expression the PIM1 kinase, ultimately mediating chemoresistance and cell survival through hypoxia-induced stress tolerance in PCa. . |
