Suppression of the tumorigenicity of prostatic cancer cells by gene(s) located on human chromosome 19p13.1-13.2.

Abstract

In previous reports, we used microcell fusion-mediated chromosomal transfer to introduce normal human chromosomes into highly metastatic rat prostatic cancer cells to map the location of tumor and metastasis suppressor genes. The gene for prostate-specific antigen as well as several classes of genes, including cell adhesion molecules, previously demonstrated to be altered during prostate cancer progression, were mapped to human chromosome 19. A normal human chromosome 19 was introduced into Dunning-R3327 AT6.1 rat and TSU-prl human prostatic cancer cells by microcell-mediated chromosome transfer to test the suppressive effects of this chromosome on prostate cancer. Five independent hybrid clones from Dunning-R3327 AT6.1 rat prostatic cancer cells and four independent hybrid clones from TSU-pr1 human prostatic cancer cells were isolated, karyotyped, allelotyped, and analyzed for in vitro and in vivo growth characteristics. Introduction of human chromosome 19 into both the rat and human prostatic cancer cells resulted in alteration of cell morphology in vitro and suppression of tumorigenicity in vivo in athymic nude mice. Highly polymorphic SSR2 markers mapped to human chromosome 19 were used to determine the portions of human chromosome 19 retained in the hybrids. These analyses identified a region localized on human chromosome 19p13.1-13.2 that is responsible for the tumor suppression of both rat and human prostatic cancer cells. The expression of several genes previously mapped to this human chromosome 19p13.1-13.2 region (i.e., ICAM-1, Notch3, and Stau) were analyzed to evaluate if they could be candidate suppressor genes for prostate cancer cell growth in vivo, but no expression patterns consistent with those predicted for a suppressor gene were observed. Human chromosome 19p13.1-13.2 contains potential tumor suppressor gene(s) for prostate cancer.