Models for development of nonreceptor methods for distinguishing androgen-sensitive and -insensitive prostatic tumors

Abstract

From the original Dunning R-3327 rat prostatic adenocarcinoma, several distinct sublines have been obtained. These sublines include a well-differentiated, slow-growing, androgen-sensitive tumor (R-3327-H); a well-differentiated, slow-growing, androgen-insensitive tumor (R-3327-HI); and a fast-growing, androgen-insensitive, anaplastic tumor (R-3327-AT). These three sublines were compared in order to develop new model methods for the prediction of the androgen sensitivity and the degree of differentiation of prostatic adenocarcinomas. The R-3327-AT was very distinct in all parameters examined except the tissue protein electrophoretic patterns which contained a uniform pattern in all tumors. The significant differences between R-3327-H and -HI sublines were (a) the inability of testosterone to stimulate DNA synthesis in the R-3327-HI tumor and (b) the difference in the enzymatic profiles of these sublines. The specific activity of three enzymes (3 alpha-hydroxysteroid dehydrogenase, leucine aminopeptidase, lactic dehydrogenase) increased while the activity of another three enzymes (6 alpha,7 alpha-hydroxylase, 5 alpha-reductase, alkaline phosphatase) decreased in the sublines which are androgen insensitive and less differentiated. An arbitrary index was constructed, based upon these enzyme differences, which clearly discriminates the degree of androgen sensitivity and differentiation of these R-3327 rat prostatic adenocarcinomas.