关键词：雄激素；肿瘤；前列腺癌；受体位点（生理学）
摘 要：Although most prostate cancers are initially responsive to androgen ablation therapy, they become treatment resistant as tumor cells develop mechanisms to evade the treatment. Early knowledge of the androgen receptor dysfunctions will help in patient stratification for emerging therapeutic strategies. We proposed an approach for monitoring potential dysfunctions of the androgen receptor by measuring expression of a panel of genes directly regulated by androgen receptor. We examined human prostate cancer tissues (surgery or diagnostic biopsy specimens) at early stages of the disease and matched with longitudinal follow up data. Within the first reporting period we have completed the quality control of detecting PSA/KLK3, PMEPA1, NKX3.1, ODC1, AMD1 and TMPRSS2-ERG genes in VCap cell culture model monitoring kinetic and dose response to androgen. In the second reporting period we have completed the qRT-PCR evaluation of in 77 patients by monitoring ERG, PSA, PMEPA1 and GAPDH levels. Also, we have completed the evaluation of 40 whole mounted sections of RP specimens by immunohistochemistry assessing AR, ERG, NKX3.1 and PSA proteins and compared the results to corresponding GeneCHip mRNA expression levels from the same tumor foci. The result indicated remarkable accuracy of the androgen regulated gene expression at mRNA levels performed better in prediction favorable outcomes in tumors with well differentiated morphology. By the completion of the proposed research we will provide a quantitative index of AR dysfunction for enhancing prognostic accuracy and to stratify patients for specific therapeutic approaches at early stages of prostate cancer treatment.