Transforming growth factor-β1 (TGF-β1) and androgen are potential physiological regulators of prostate cancer cells. In the present study, we have used LNCaP cells as a model of androgen-responsive prostate cancer to investigate the effects of dihydrotestosterone (DHT) on the sensitivity to TGF-β1. The ability of LNCaP cells to respond to TGF-β has been controversial. In some studies, LNCaP cells were insensitive to TGF-β1 while, in others, they were sensitive to the growth inhibitory effect of TGF-β1. The present study was carried out to establish androgenic conditions that rendered LNCaP cells sensitive to TGF-β1. Cells were cultured in phenol-red-free RPMI 1640 medium supplemented with 10% charcoal-stripped fetal bovine serum. DHT was added at the following concentrations: 0, 10-12, 10-10, and 10-7 M. These concentrations were selected because they represent the zero DHT control, the low-proliferative dose, the high-proliferative dose, and the growth-arrest dose, respectively. The effects of TGF-β1 observed on LNCaP cells included inhibition of cell proliferation, decrease in cell viability, alteration in cell morphology, and enhancement of gene transcriptional activity through activation of a TGF-β responsive promoter. Of the various DHT concentrations investigated in this study, these effects of TGF-β1 on LNCaP cells were consistently demonstrated only at 10-10 M. At other concentrations, the effects of TGF-β1 were either minimal or undetectable. Accompanying these effects of TGF-β1, a low but statistically significant level of TGF-β1-specific binding and an increased protein level of TGF-β receptor type II were detected by a competitive binding assay and Western blot analysis, respectively. These results indicate that LNCaP cells can be induced by DHT to respond to TGF-β1 and that DHT modulates the sensitivity to TGF-β1 and the level of TGF-β receptor type II in these Cells.
ASJC Scopus subject areas
- Cell Biology