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) receptor, p185erbB‐2 and transforming growth factor‐α (TGF‐α) levels were examined in prostatic adenocarcinoma. Male nude mice were inoculated with the CWR22 androgen‐dependent human prostatic tumor or an androgen‐independent (CWR22R) derivative. Mice with CWR22 tumors were castrated and subsequently killed at 3, 7, 21, 28 or 42 days post‐castration. Other CWR22‐bearing mice received s.c. testosterone pellets at 21 days post‐castration and were killed 7 days later. EGF receptor, p185erbB‐2 and TGF‐α levels were examined by immuno‐histochemistry. Strong EGF receptor and p185erbB‐2 immunostaining was detected in CWR22 tumors from intact controls. EGF receptor immunostaining decreased by 65% to 70% at 21 to 42 days post‐castration. Testosterone treatment at 21 to 28 days post‐castration resulted in a 2‐fold increase in EGF receptor immunostaining. p185erbB‐2 immunostaining within 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 p185erbB‐2 levels were confirmed by Western blot analysis. Fewer than 10% of CWR22 tumor cells demonstrated strong TGF‐α immunostaining, and androgen manipulation did not effect TGF‐α immunostaining. In contrast, 30% of androgen‐independent CWR22R tumor cells were strongly immunostained for TGF‐α. Our findings indicate that EGF receptor levels, but not p185erbB‐2 levels, are strongly dependent on testosterone in CWR22 tumors. The co‐localization of TGF‐α and the EGF receptor in CWR22R tumors suggests that these factors may constitute an autocrine pathway that regulates androgen‐independent growth. Int. J. Cancer 82:424–429, 1999. © 1999 Wiley‐Liss, Inc.