Androgen independent epithelial cells of the rat ventral prostate.

Abstract

The human prostate is a secondary sexual organ that requires an uninterrupted supply of androgens to maintain structural and functional integrity of androgen dependent epithelial cells. Eventual failure of hormonal therapies for prostate cancer is often attributed to the presence of androgen independent epithelial cells in the tumor. Using the rat ventral prostate as a model of the human prostate, we have isolated and characterized an androgen independent epithelial cell population present in the normal rat ventral prostate. These cells grow very quickly and have been termed Rapidly-Dividing Epithelial (RDE) cells. The RDE cells are completely independent of androgens for cell survival and do not secrete the androgen dependent secretory proteins, secretory acid phosphatase and prostate steroid binding protein. The epithelial cell origin of RDE cells was confirmed by cytokeratin expression, testosterone metabolism patterns and by purification parameters. Culture with various differentiation-inducing agents resulted in major morphological changes and structures reminiscent of those in the mature prostate but not in the expression of androgen-dependent secretory products. RDE cells demonstrate a very high in-vitro propensity for transformation yet no tumor growth in-vivo. None of the ten common "immortalizing" proto-oncogenes tested were expressed. RDE cells appear to be the rat counterpart to androgen-independent epithelial cells which cause renewed tumor growth in prostate cancer patients treated by hormonal therapies.