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Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611 [I. Y. K., D. J. Z., J. W. S., J. A. S., J-H. K., C. L.]; Department of Urology, College of Medicine, University of Ulsan, Asan Medical Center, 388-1 Poonynap-Dong, Songpa-Gu, Seoul, Korea [H-J. A.]; and Department of Biochemistry, The Cancer Institute, Kami-ikebukuro 1-37-1, Toshima-ku, Tokyo, Japan [M. K.]
Transforming growth factor ß1 (TGF-ß1), a potential regulator of growth of prostate cancer cells, exerts its effects through interaction with membrane receptors. In the present study, an attempt was made to establish a correlation between TGF-ß1 sensitivity and TGF-ß receptor expression in three prostate cancer cell lines (PC3, DU145, and LNCaP). In a dose-dependent manner, TGF-ß1 inhibited the proliferation of PC3 and DU145 cells but not LNCaP cells. Since TGF-ß signals through a heteromeric complex composed of TGF-ß receptors type II and type I, the expression of these receptors was investigated by Western blot analysis and reverse transcriptase-PCR. These studies demonstrated that all three prostate cancer cell lines express type II receptor. In contrast, type I receptor was detected only in the TGF-ß1-sensitive PC3 and DU145 cells but not in the TGF-ß1-insensitive LNCaP cells. To investigate the possibility that the undetectable expression of type I receptor in LNCaP cells is due to a change in the respective gene, Southern blot analysis was performed. The result demonstrated that there was a genetic change in type I receptor gene in these cells. Subsequently, when LNCaP cells were transiently transfected with TßR-I cDNA, sensitivity to TGF-ß1 was restored. These observations indicate that LNCaP cells contain a defective TßR-I gene which rendered these cells insensitive to the action of TGF-ß1.
1 This work was supported in part by NIH Grants DK 39250, CA 69851, and CA 60553.
2 To whom requests for reprints should be addressed, at Tarry 11–715, Department of Urology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611. Phone: (312) 908-2916.
Received 10/13/95. Accepted 11/13/95.
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