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Autonomous Growth of Androgen-independent Human Prostatic Carcinoma Cells: Role of Transforming Growth Factor ¹

Urological Oncology Program, Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611 [D. R. H., E. R. S., W. D. B., C. L., J. M. K.], and Laboratory of Receptor Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [J. M.]

The androgen-independent prostatic carcinoma cell line PC3 is known to exhibit autonomous growth in vitro and in vivo. The purpose of the present study was to investigate the role of transforming growth factor (TGF-) and its receptor, the epidermal growth factor (EGF) receptor, in the regulation of PC3 cell proliferation. Results showed that PC3 cells secrete factors into conditioned medium that are mitogenic for the less aggressive prostatic carcinoma lines DU145 and LNCaP. Gel filtration chromatography of PC3-conditioned medium revealed a major peak of mitogenic activity at a molecular weight of 5,000 to 10,000 which was inhibited by the addition of antibody to TGF-. The synthesis and secretion of TGF- by PC3 cells were further demonstrated by immunoblotting and radioimmunoassay. Radioreceptor analysis showed a single class (K_d 5.3 nM) of EGF receptors on PC3 cells. The presence of M_r 170,000 EGF receptors on PC3 cells was further demonstrated by immunoprecipitation of metabolically labeled proteins. TGF- was effective in stimulating the growth of low-density, but not high-density, PC3 cultures. In addition, the proliferation of PC3 cells under serum-free defined conditions was inhibited by antibodies to TGF- and/or the EGF receptor. These data indicate that TGF-/EGF receptor interactions are partially responsible for autonomous growth of the PC3 cell line and may explain one mechanism of escape from androgen-dependent growth in human prostatic carcinoma.

¹ Supported, in part, by NIH Grant DK39250, Contract CM97628 from the National Cancer Institute, and the Lucy and Edwin Kretschmer Fund of Northwestern University Medical School.

² Recipient of NIH Postdoctoral Fellowship DK08204 and the William O. Jeffery III Fellowship for Prostate Cancer Research of Northwestern University Medical School. To whom requests for reprints should be addressed.

Received 11/28/90. Accepted 3/14/91.

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