Differentiation and stromal-induced growth promotion of murine prostatic tumors

BACKGROUND. We have derived a panel of p53-null prostatic basal and luminal epithelial cell lines and their ras transformed counterparts to study stromal/epithelial interactions and the properties of tumors arising from basal and luminal cells. METHODS. Previously derived normal murine prostatic basal epithelial (PE-B-1) and luminal epithelial (PE-L-1) cell lines were transformed with. N-Ras. These lines and a spontaneously transformed luminal cell line were inoculated subcutaneously or orthotopically into athymic mice, alone or in combination with normal prostatic smooth muscle cells (SMC). RESULTS. All transformed lines formed subcutaneous tumors, SMC significantly enhanced the growth rate of the tumors arising from the basal and one of the luminal cell lines. The transformed basal line gave rise to tumors expressing both basal and luminal cytokeratins. CONCLUSIONS. Prostatic SMC promote the growth of transformed epithelial cells, suggesting that prostatic stroma may promote tumor development, Furthermore, transformed basal cells give rise to tumors containing luminal cells, suggesting that although most human tumors have a luminal phenotype, they may originate from transformed basal cells. (C) 2002 Wiley-Liss, Inc.