Epidemiological and preclinical studies suggest that dietary and hormonal factors are likely contributors to the initiation and progression of prostate cancer. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), derived from cooked meat, is known to induce prostate cancer in the rat. We used 2D-DIGE and LC/MS/MS technologies to identify proteins that show altered expression after treatment of rat prostate lobes with 10-3 M 2-N-hydroxylamino-1-methyl-6-phenylimidazo[4,5-b]pyridine (NOH-PhIP), 10-7 M 5\#945;-dihydrotestosterone (DHT), individually and in combination. Eight candidate protein spots detected by 2D-DIGE in at least two out of three lobes showed greater than or equal to two-folds difference between treated and control samples. Five out of the eight spots contained single proteins; including, phospholipase C\#945; (PLP-C\#945;), Rab7, SAR1a, ribosomal protein S7 (RPS7), and nucleoside diphosphate kinase (NDPK). The altered expression of NDPK was validated by western blot analysis. The concordance between 2D-DIGE and western analysis for NDPK was 80%, and our results are in accord with published literature which shows that NDPK expression is altered in human cancers, including prostate cancer. This study demonstrates that the combination of 2D-DIGE with LC/MS/MS is a powerful tool for identification of proteins in the prostate tissue that are altered by environmental carcinogens (NOH-PhIP) and hormones (DHT). Support: CA 127729

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1211.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO