Molecular and Cellular Endocrinology 153 (1999) 29 – 38 Retinoid and androgen regulation of cell growth, epidermal growth factor and retinoic acid receptors in normal and carcinoma rat prostate cells Frank Richter a , Hosea F.S. Huang a,c, *, Ming-tang Li a , David Danielpour d , Shoou-Lih Wang b , Robert J. Irwin Jr. a a Department of Surgery Section of Urology, UMD-New Jersey Medical School, 185 South Orange Ae, MSB G-506, Newark, NJ 07103, USA b New Jersey Dental School, 185 South Orange Ae, Newark, NJ 07103, USA c V.A. Medical Center, East Orange, NJ 07019, USA d Laboratory of Chemopreention, National Cancer Institute, Bethesda, MD 20892, USA Received 17 January 1999; accepted 2 April 1999 Abstract Recent in vivo and in vitro studies suggest that retinoic acid receptor (RAR)-mediated processes may be involved in androgen regulation of prostate cells in a manner that may be altered during prostatic carcinogenesis. We tested this hypothesis in the newly established carcinoma and non-carcinoma rat prostate epithelial cell lines, NRP-154 and NRP-152, respectively. In DMEM/F-12 medium supplemented with 10% charcoal stripped fetal calf serum (cFCS), the number of both NRP-152 and NRP-154 cells were stimulated by testosterone (T), with a 4-fold greater effect in NRP-152 than in NRP-154 cells. Retinoic acid (RA) alone also stimulated the growth of NRP-152 cells, but failed to induce cell growth of NRP-154 cells. Importantly, the level of RAR  mRNA was elevated whereas the levels of RAR  and androgen receptor (AR) mRNA were lower in NRP-154 cells compared to those in NRP-152 cells. Treatment of NRP-152 cells with increasing doses of T resulted in a dose-dependent decrease and rebound of the level of RAR  and  mRNA in NRP-152 cells; these effects were not apparent, if not reversed, in NRP-154 cells. Both ligand binding and Western blot analyses revealed that epidermal growth factor receptor (EGF-R) was stimulated by 20 nM T but was suppressed by 0.1 M RA, which also attenuated the stimulating effects of T on EGF-R in NRP-152 and to a lesser extent in NRP-154 cells. The differences in the level and androgen regulation of RAR mRNAs and reciprocal regulation of EGF-R expression by T and RA between NRP-154 and NRP-152 cells suggest that variations in the EGF-R and RAR signal events may contribute to differences in growth rate between these two cell lines. © 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Androgens; EGF-R; Prostate cancer; Retinoic acid receptor 1. Introduction Androgen and vitamin A are both essential for nor- mal functions of the prostate. Androgen deprivation results in the regression of the prostate, attributable to an increase in cell death and cessation of cell prolifera- tion (Kyprianou and Isaacs, 1988; Lee et al., 1990). On the other hand, androgen is also implicated in the pathogenesis of benign and/or malignant prostatic hy- perplasia (Whitmore, 1973; Lee et al., 1995). The prostate also regresses during vitamin A deficiency and is characterized by metaplasia of the epithelial cells (Wolbach and Howe, 1925); such changes can be pre- vented by retinoic acid or retinol (Thompson et al., 1964). These results, and recent reports of prevention of chemical-induced prostate carcinogenesis by retinoic acid (RA) and its analogs (Pollard et al., 1991; Pienta et al., 1993; Stearns et al., 1993), suggest that retinoids may have a critical role in the maintenance of normal differentiation of prostate cells. Both androgens and retinoids initiate their biologic functions by binding to and activation of respective nuclear receptors, androgen receptor (AR) and retinoic * Corresponding author. Tel.: +1-973-972-7728; fax: +1-973-972- 6803. 0303-7207/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved. PII:S0303-7207(99)00095-7