Contributions of 8P Loss and 8Q Gain to the Malignant Phenotype in Human Prostate Tumors

摘要

Prostate cancer research is hampered by the lack of suitable human in vitro models that accurately recapitulate the genetic composition or biological behavior of initiate primary prostate tumors. In order to overcome this limitation, the Nl5C6 epithelial and the Nl fibroblastic cell lines were developed through immortalization of explanted human prostate tissue with the HPV and E6 and E7 proteins. Genotypic characterization revealed that immortalization of the Nl5C6 epithelial cells was associated with a dominant genetic alteration involving the short arm of chromosome 8, a region often deleted or rearranged in primary human prostate tumors. Phenotypic characterization demonstrated that the Nl5C6 epithelial and Nl fibroblastic cell lines expressed cell-type appropriate proteins and gene transcripts. The Nl5C6 cells, but not Nl cells, expressed anchorage independence, consistent with an initially transformed phenotype. Moreover, Nl5C6 epithelial cells proliferated and formed colonies in soft agar at rates 2-3 fold higher when grown in Nl fibroblast conditioned serum free media compared to unconditioned serum free media. These results suggest that factors secreted by Nl fibroblasts augmented expression of the malignant phenotype by Nl5C6 epithelial cells, and show that paracrine interactions defined the malignant potential of transformed epithelial cells in the human prostate.