TY - JOUR
T1 - Modulation of sensitivity to transforming growth factor-β1 (TGF-β1) and the level of type II TGF-β receptor in LNCaP cells by dihydrotestosterone
AU - Kim, Isaac Yi
AU - Zelner, David J.
AU - Sensibar, Julia A.
AU - Ahn, Han Jong
AU - Park, Linda
AU - Kim, Jin Ho
AU - Lee, Chung
N1 - Funding Information:
1This work was supported in part by NIH Grants DK 39250 and CA 60553.
PY - 1996/1/10
Y1 - 1996/1/10
N2 - 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.
AB - 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.
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U2 - 10.1006/excr.1996.0013
DO - 10.1006/excr.1996.0013
M3 - Article
C2 - 8549651
AN - SCOPUS:0030062368
SN - 0014-4827
VL - 222
SP - 103
EP - 110
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 1
ER -
