RAT PROSTATE-CANCER CELLS CONTAIN FUNCTIONAL RECEPTORS FOR TRANSFORMING GROWTH FACTOR-BETA

Clonally derived C-, D-, and T-family AXC/SSh rat prostate cancer cell lines contain transforming growth factor- β‪ (TGFβ‪) receptors. The content in C3, Dl, Tl, and T5 cells, respectively, was 8, 560 ± 1, 450, 13, 160 ± 1, 240, 2, 425 ± 490, and 10, 540 ± 1, 025 sites/cell (mean ± SEM). Respective Kd values were 160 ± 48, 200 ± 53, 24 ± 3, and 115 ± 15 pM (mean ± SEM). Tl cell TGFβ‪ receptor site content and Kddiffered significantly from those of other prostate cancer cell lines (P < 0.05). TGFβ is a bifunctional concentration-dependent modulator of Tl and T5 cell thymidine incorporation. At low concentrations, thymidine incorporation was inhibited, whereas as the medium TGFβ content was increased, Tl and T5 cell thymidine incorporation was stimulated. The concentrations of TGFβ‪ causing half-maximum inhibition of Tl or T5 cell thymidine incorporation, respectively, were 0.11 and 0.24 pM, whereas the respective TGFβ‪ concentrations causing half-maximum stimulation of thymidine incorporation were 14.4 and 134 pM. These findings establish that rat prostate cancer cell sensitivity to TGFβ‪ inhibition of function is at least 2 orders of magnitude greater than that of most other mammalian cells. In contrast, the sensitivity of rat prostate cancer cells to TGFβ‪ enhancement of function is comparable to that of other mammalian cells. TGFβ‪ inhibited basic fibroblast growth factor (bFGF) stimulation of Tl and T5 cell thymidine incorporation. Because the concentration of bFGF required for half-maximum increase of T5 cell thymidine incorporation was independent of medium TGFβ‪ content, the effect of TGFβ‪ is distal to the T5 cell bFGF receptor. In contrast, the concentration of bFGF required for half-maximum increase in Tl cell thymidine incorporation increased 5-fold as the medium TGFβ‪ content was increased; suggesting that the effect of TGFβ‪ in Tl cells is proximal to the Tl cell bFGF receptor. Our studies establish that rat prostate cancer cells contain functional TGFβ‪ receptors, imply the presence of functional bFGF receptors, and demonstrate that mitogen modulation of prostate cancer cell function is multifactorial.The finding that TGFβ‪ is a bifunctional effector of prostate cancer cell DNA synthesis provides some insight into the potential complexity of mitogen modulation of prostate cancer cell proliferation. The mechanism by which these mitogens interact is unknown; however, our studies suggest that some interactive effects may be cell line specific. © 1990 by The Endocrine Society.