|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1997 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1996 : ¥1,500,000 (Direct Cost : ¥1,500,000)
To explore the molecular abnormalities in human prostate carcinome, the genomic DNAs extracted from 3 prostate cell lines-LNCaP,PC-3 and DU-145-were examined using restriction landmark genomic scanning (RLGS) methodology, a 2-dimensional gel analysis which allows evaluation of approximately, 2,000 Not I landmarks. The 24,18 and 23 amplified spots were detected in LNCaP,PC-3 and DU-145 DNA,respectively. Eleven spots were commonly intensified in all 3 cell lines, with a range of amplification of 2.1 to 134.1-fold over normal. Alterations in the genomic DNAs of 6 heterogeneous prostate carcinomas, as well as that of indiviual and histologically distinct foci within the tumors, were examined. In this study, comparison of cancer DNAs against normal prostate DNA controls yielded alterations in at least 35 spots. Despite differences in the histological grading of tumors, 3 spots common to all tumor samples showed consistent amplification of intensity and 8 other common spots demonstrated consistent reduction of intensity when compared to control. In addition, spot alterations occurred between histologically identical foci isolated from within single tumors. It is suggested that these spot changes detected in RLGS-generated DNA profiles reflect aberrations in as yet unidentified oncogenes and tumor suppressor genes, and indicate, as well, that prostate cancer is not only histologically heterogeneous and multifocal but also genetically multicentric.
On the contrary, within each of the 16 hyperplasias examined, 2 to 10 spots were found with altered intensities, as compared to equivalent spots from normal prostate, but could detect few common spot profiles for any hyperplasia samples. There may be no consistent genetic changes in the pathogenesis of some forms of human benign prostatic hyperplasia. These results suggest that common genetic abnormalities may occur in carcinomas of the human prostate.