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Regulation of Apoptosis Induced by Transforming Growth Factor-ß1 in Nontumorigenic and Tumorigenic Rat Prostatic Epithelial Cell Lines

Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892

Transforming growth factor-ß1 (TGF-ß1), which is induced in the prostate following castration, has been speculated to mediate apoptosis of epithelial cells during prostatic involution. Here, we report the first evidence of a direct effect of TGF-ß on induction of apoptosis in prostatic epithelial cells in vitro, using NRP-152 nontumorigenic and NRP-154 tumorigenic rat prostatic epithelial cell lines. TGF-ß1 induces apoptosis of both cell lines within 24 h, as shown by a decrease in cell viability, in situ DNA nick-end labeling, and internucleosomal DNA fragmentation. Moreover, the ability of TGF-ß to induce apoptosis of NRP-152 is strictly dependent on culture conditions, because dexamethasone enhances while insulin and insulin-like growth factor-I specifically block apoptosis induced by TGF-ß. We suggest that TGF-ßs are direct physiological regulators of apoptosis of prostatic epithelial cells.

¹ Both authors contributed equally to this work.

² Supported by a predoctoral intramural research training award from the NIH.

³ Present address: Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-Cho, Showa-Ku, Nagoya 466, Japan.

⁴ Supported by a summer training research award from the NIH.

⁵ To whom requests for reprints should be addressed, at Laboratory of Chemoprevention, Building 41, Room C629, 9000 Rockville Pike, National Cancer Institute, NIH, Bethesda, MD 20892-5005. Phone: (301) 496-8349; Fax: (301) 496-8395.

Received 9/11/96. Accepted 10/ 3/96.

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