E1A TRANSFORMED NORMAL HUMAN PROSTATE EPITHELIAL-CELLS CONTAIN A 16Q DELETION

The difficulty of maintaining long-term prostate cell cultures has hin dered the development of essential models for understanding prostate c ancer. We report here the establishment of two 12S E1A transformed non -tumorigenic prostate epithelial cell strains, and their characterizat ion. The two clonal cell strains, TP2 and TP4, proliferated for approx imately 40 passages before senescence. Both exhibited a strong depende nce on exogenous peptide growth factors and an immunophenotype charact eristic of their prostate epithelial origin. Cytogenetic analysis reve aled a consistent deletion on the q arm of chromosome 16 in TP2 with a n otherwise normal karyotype. Band-specific microdissection generated region-specific probes from 16q23, which when used in fluorescence in situ hybridization (FISH) revealed that the region was deleted in 83% of metaphases analyzed. By cytogenetic analysis and FISH, the q arm of 16 was found deleted from the genome of TP4 in 60% of cells analyzed. Lost sequences on 16q-16q23 in particular-in prostate cancer have bee n observed by a variety of methods. Localization of common region of d eletion has been determined from these studies to be distal to 16q23. Our findings suggest that 16q23 may be of major importance in the deve lopment of prostate cancer, and may harbor tumor suppressor elements. (C) Elsevier Science Inc., 1998.