Identification of New EGR1 Target Genes That Regulate Radiation Responses in Prostate Cancer Cells

摘要

I have studied the induction of early stress response gene, Egr1, under various stress conditions in prostate cancer cells. I chose the induction of these cells by UV treatment for identifying target genes of Egr1 under this stress condition. I used ChIP on Chip (using promoter arrays) to identify these target genes. I helped in preparation of these promoter arrays which have +12, 000 promoter sequences on them and then went ahead to standardize all the protocols to achieve minimum false positive results. These experiments helped me to identify various known and unknown targets of Egr1 such as IGF1, MAP2K1, CDKNIB, CCNB2, ADAR and PAX3. We identified 177 target genes after the statistical analysis and verified that at least 68% of them contained Egr1 binding consensus sites in their promoters. Ten of these genes were validated by conventional Chip and by Q-RT-PCR analysis. The major pathways involved were Tissue Development/Cellular Movement/Gene Expression, Cell Death, Cell Cycle, Cell Signaling, Cellular Development, Cancer/Cell-To-Cell Signaling and Interaction. The results show that Egr1 induction upon UV irradiation leads to a cascade of events in prostate cancer cells. Further studies on these target genes are underway to study the effect of these genes after irradiation of cells.