Epigenetic regulation of gene expression in cervical cancer cells by the tumor microenvironment.

摘要: Evidence is accumulating that the adverse tumor microenvironment both modifies malignant progression of cells and contributes to chemotherapy radiation resistance. We hypothesized some effects on are mediated through transcriptional regulation genes responsive stresses microenvironment, such as low oxygen or glucose conditions. To determine epigenetic changes in gene expression were consistent with hypothesis, we used an vitro subtractive hybridization method, representational difference analysis, identify hypoxia-induced cDNAs from cultured human cervical epithelial cells. identified 12 induced genes: two novel (HIG1 HIG2), three known be hypoxia-inducible (tissue factor, GAPDH, thioredoxin), seven not previously [HNRNP(a1), ribosomal L7, annexin V, lipocortin 2, Ku(70), PRPP synthase, acetoacetyl-CoA thiolase]. In cells, HIG1 HIG2 by hypoxia deprivation, but their serum UV, ionizing radiation. The putative open reading frames expressed confirmed epitope tagging. addition, xenografts derived cancer display increased when they deprived oxygen. Taken together, these data suggest a coordinated response eukaryotic microenvironmental found solid tumor.