DNA-PLOIDY AND CLONAL SELECTION IN RAS PLUS MYC-INDUCED MOUSE PROSTATE-CANCER

An important goal in prostate cancer research is to define specific mo lecular and cellular alterations that are associated with malignant pr ogression. The mouse prostate reconstitution model is a relevant and u seful system as it allows the study of early events in cancer progress ion under conditions where oncogene-initiated cells are surrounded by normal tissue. Using this model, activated ras and myc oncogenes are i ntroduced into urogenital sinus cells via the recombinant retrovirus Z ipras/myc 9. After 4 weeks' growth as subcapsular renal grafts, poorly differentiated carcinomas are produced in C57BL/6 mice. In this study we examined the temporal relationships between morphological alterati ons, growth, DNA ploidy status and clonal selection as determined by S outhern blotting in ras + myc-initiated carcinomas. Nuclear image anal ysis demonstrated that the emergence of a cycling DNA tetraploid cell population strongly correlated with growth and histologic progression. These tightly linked events culminated in the outgrowth of mono- or o ligoclonal cancer. (C) 1995 Wiley-Liss, Inc.