Evaluation of the putative tumor suppressor gene FHIT in prostate carcinoma

Prostate, cancer is the must frequenlU diagnosed cancer among men in t he United States. Like other neoplastic diseases, prostate cancer undergoes ;i complement of genetic alterations thai are not yet understood. About ")-10'X of all prostate cancer and more t h an 10c/t ol early-onset prostate cancer is familial, with Mendelian inheritance. Man> chromosomal alterations are involved in prostate cancer, including the short arm of chromosome il (Up). The FHI'l {fragile histidine triad) gene, located at ;ipl-1.2 and encompassing the FRA-4li fragile site, was recently cloned and characterized. FHIT is frequently deleted and altered in many human cancers. Loss of ho.teroJ.ygosity at the FHIT locus has led to the proposal that FHIT is a tumor suppressor gene. We investigated t lie status and function of the FHIT gene in the etiology of prostate carcinoma RT-POR analysis of total RNA from four prostate cancer cell lines, I.M'aP. I)1T MS. PC3 and S7 showed alternate transcripts formed from the FHIT gene, while no alternate transcripts were observed from the normal human prostate epithelial cells. Upon cloning of the cDNA and determining the I)NA sequence, we observed specific deletions and insertions in the alternate transcripts, the net result of which is loss of coding exons. In other cases, we find insertion of single bases that may result in disruption of the reading frame. As a tumor suppressor gene. FHIT gene alterations may predispose an individual to tin1 development of prostate cancer. lo investigate if FHIT is a tumor siipprossui gene in prostate cancer, we are conducting microsatellile deletion analysis UM nj.>, a in ntro model system foi prostate r;incer.