Isolation and functional analysis of differentially expressed genes in human prostate cancer

摘要: Prostate cancer is the most frequently diagnosed solid tumor in men, and second leading cause of death males from western countries. One key issues prostate research to develop molecular markers that can effectively detect distinguish progression malignancy tumors as well provide insights into development or behaviour. As insulin-like growth factor I receptor (IGF-IR) was reported play an important role cellular homeostasis carcinoma, antisense RNA strategy employed reduce endogenous IGF-IR gene expression human carcinoma PC-3 cells resulting a significant suppression cell invasion proliferation increase apoptosis. Furthermore, it demonstrated direct correlation exists between inhibition up-regulation IGFBP-3 down-regulation MMP-2 androgen-independent cells. In addition, both were investigated by quantitative real time RT-PCR analyses on LCM-derived matched normal epithelial tissue samples 12 patients demonstrating up-regulated cancers (9 out 12) down-regulated all carcinomas. using profiling array determined following cancers: kidney cancer, lung rectum colon stomach thyroid whereas breast uterus ovarian cancer. These results indicate for further basis targeting potential treatment better understanding IGF-IR-activated signaling pathways. Next, order analyze differential putative levels more than 400 cancer-related genes compared cDNA technique set tissue. total, 46 differentially expressed identified be up- carcinoma. From these genes, seven (Bax inhibitor-1 ,complement component C1s, ferritin heavy chain, MAT8 protein, peptidyl-proryl cis-trans isomerase A, RNA-binding protein regulatory subunit DJ-1 vacuolar ATP synthase F) displaying confirmed overexpressed analysis whole RNA. The overexpression Bax (BI-1) Northern blot thirteen laser captured microdissected samples. BI-1 uterus, determine function vitro, androgen-dependent LNCaP transfected with small interfering double-stranded (siRNA) oligonucleotides against specific expression. Moreover, transfection sequence-specific siRNAs caused apoptosis necrosis. Taken together, present contains serve marker novel target developing therapeutic strategies