Rat Prostate Cancer Cells Contain Functional Receptors for Transforming Growth Factorβ*

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Abstract
Clonally derived C-, D-, and T-family AXC/SSh rat prostate cancer cell lines contain transforming growth factor-.beta. (TGF.beta.) receptors. The content in C3, D1, T1, and T5 cells, respectively , was 8,560 .+-. 1,450, 12,160 .+-. 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). T1 cell TGF.beta. receptor site content and Kd differed significantly from those of other prostate cancer cell lines (P < 0.05). TGF.beta. is a bifunctional concentration-dependent modulator of T1 and T5 cell thymidine incorporation. At low concentrations, thymidine incorporation was inhibited, whereas as the medium TGF.beta. content was increased, T1 and T5 cell thymidine incorporation was stimulated. The concentrations of TGF.beta. causing half-maximum inhibition of T1 or T5 cell thymidine incorporation., respectively, were 0.11 and 0.24 pM, whereas the respective TGF.beta. concentrations causing half-maximum stimulation of thymidine incorporation were 14.4 and 134 pM. These findings establish that rat prostate cancer cell sensitivity to TGF.beta. 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 TGF.beta. enhancement of function is comparable to that of other mammalian cells. TGF.beta. inhibited basic fibroblast growth factor (bFGF) stimulation of T1 and T5 cell thymidine incorporation. Because the concentration of bFGF required for half-maximum increase of T5 cell thymidine incorporation was independent of medium TGF.beta. content, the effect of TGF.beta. is distal to the T5 cell bFGF receptor. In contrast, the concentration of bFGF required for half-maximum increase in T1 cell thymidine incorporation increased 5-fold as the medium TGF.beta. content was increased; suggesting that the effect of TGF.beta. content was increased; suggesting that the effect of TGF.beta. in T1 cells is proximal to the T1 cell bFGF receptor. Our studies establish that rat prostate cancer cells contain functional TGF.beta. receptors, imply the presence of functional bFGF.beta. receptors, and demonstrate the mitogen modulation of prostate cancer cell function is multifact orial. The finding that TGF.beta. 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.

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