Background: Epidermal growth factor (EGF) and interleukin (IL)-6 are implicated in the growth of benign and malignant prostatic epithelial cells. We investigated the role of EGF and IL-6 during the process of prostate carcinogenesis.
Methods: Using growth in soft agar as an index of transformation, we examined the effect of EGF and IL-6 on the enhancement of N-methyl-N-nitrosourea (MNU)-initiated transformation of immortalized, nontumorigenic prostatic epithelial cell lines (PWR-1E and RWPE-1) developed in our laboratory. The effect of EGF and IL-6 on the growth of MNU-induced transformants isolated from soft agar was assessed both in monolayer culture and in a soft agar.
Results: After a 1 hr exposure to N-methyl-N-nitrosourea (50 microg/ml), cells (5 x 10(4)) were grown in soft agar in the presence of EGF (5 ng/ml) or IL-6 (10 or 100 ng/ml). Addition of EGF or IL-6 significantly increased colony formation in soft agar of both immortalized prostatic epithelial cell lines initiated with MNU (P < 0.001-0.05). Only a very small number of colonies was observed with the parental cell lines PWR-1E and RWPE-1 not exposed to MNU, and their numbers increased by the addition of EGF or IL-6. All of the transformants, derived by exposure to MNU and isolated from soft agar, exhibited a higher cell growth potential in monolayer cultures than did their parental cell lines. Furthermore, as compared to the parental cell lines, growth response of MNU-transformants to 5alpha-dihydrotestosterone (5alpha-DHT), EGF, or IL-6 in monolayer culture was better in 5 of 8, 6 of 8, and 7 of 8 cell lines, respectively. All of the MNU-transformants exhibited a far higher colony-forming efficiency in soft agar than did the parental cell lines. However, the degree of responsiveness to EGF or IL-6 in soft agar varied among the MNU-transformants.
Conclusions: The results of the present study suggest that IL-6 and EGF may enhance prostate carcinogenesis in vitro by preferentially stimulating the growth of transformed cells.