Interleukin-6 and epidermal growth factor promote anchorage-independent growth of immortalized human prostatic epithelial cells treated withN-methyl-N-nitrosourea
✍ Scribed by Okamoto, Masato; Webber, Mukta M.; Quader, Salmaan; Oyasu, Ryoichi
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 335 KB
- Volume
- 35
- Category
- Article
- ISSN
- 0270-4137
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✦ Synopsis
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 g/ml), cells (5 × 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 5␣-dihydrotestosterone (5␣-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.