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Autocrine Effect of Androgen on Proliferation of an Androgen Responsive Prostatic Carcinoma Cell Line, LNCAP: Role of Interleukin-6

Departments of Pathology (M.O., R.O.) and Urology (C.L.), Northwestern University Medical School, Chicago, Illinois 60611-3008

Address all correspondence and requests for reprints to: Ryoichi Oyasu, M.D., Northwestern University Medical School, Department of Pathology, 303 East Chicago Avenue, Chicago, Illinois 60611-3008.

LNCaP is an androgen-responsive prostatic carcinoma cell line that exhibits a bell-shaped growth response curve to increasing doses of dihydrotestosterone (DHT) in culture. Although the precise mechanism responsible for this unique growth response to androgen stimulation remains unclear, many studies have suggested that androgen modulates the level of various growth factors. In an early study, we demonstrated that LNCaP proliferation was stimulated by interleukin (IL)-6 in a paracrine manner, because these cells did not express a significant amount of IL-6. In the present study, the role of IL-6 in mediating androgen regulated proliferation in LNCaP cells was investigated. DHT, at increasing doses up to 10^-8 M, resulted in a release of IL-6 from LNCaP cells. This dose-dependent effect of DHT on LNCaP proliferation could be partially inhibited by the addition of antibody against IL-6 into the culture medium. These results indicate that the DHT-induced expression of IL-6 stimulates proliferation of LNCaP cells in culture in an autocrine manner.

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