Androgenic regulation of growth factor and growth factor receptor expression in the CWR22 model of prostatic adenocarcinoma

The effects of androgen manipulation on epidermal growth factor (EGF) recep tor, p185(erbB-2) and transforming growth factor-alpha (TGF-alpha) levels w ere examined in prostatic adenocarcinoma. Male nude mice were inoculated wi th the CWR22 androgen-dependent human prostatic tumor or an androgen-indepe ndent (CWR22R) derivative. Mice with CWR22 tumors were castrated and subseq uently killed at 3, 7, 21, 28 or 42 days post-castration. Other CWR22-beari ng mice received s.c. testosterone pellets at 21 days post-castration and w ere killed 7 days later. EGF receptor, p185(erbB-2) and TGF-alpha levels we re examined by immuno-histochemistry. Strong EGF receptor and p185(erbB-2) immunostaining was detected in CWR22 tumors from intact controls. EGF recep tor immuno staining decreased by 65% to 70% at 21 to 42 days post-castratio n. Testosterone treatment at 21 to 28 days post-castration resulted in a 2- fold increase in EGF receptor immunostaining. p185(erbB-2) immunostaining w ithin CWR22 tumors did not decrease following castration and, in fact, was slightly increased at 7 days post-castration. The effects of castration on EGF receptor and p185(erbB-2) levels were confirmed by Western blot analysi s. Fewer than 10% of CWR22 tumor cells demonstrated strong TGF-alpha immuno staining, and androgen manipulation did not effect TGF-alpha immunostaining . In contrast, 30% of androgen-independent CWR22R tumor cells were strongly immunostained for TGF-alpha. Our findings indicate that EGF receptor level s, but not p185(erbB-2) levels, are strongly dependent on testosterone in C WR22 tumors. The co-localization of TGF-alpha and the EGF receptor in CWR22 R tumors suggests that these factors may constitute an autocrine pathway th at regulates androgen-independent growth. Int. J. Cancer 82:424-429, 1999. (C) 1999 Wiley-Liss, Inc.