Modulation of sensitivity to transforming growth factor-beta 1 (TGF-beta 1) and the level of type II TGF-beta receptor in LNCaP cells by dihydrotestosterone.
Transforming growth factor-beta 1 (TGF-beta 1) 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-beta 1. The ability of LNCaP cells to respond to TGF-beta has been controversial. In some studies, LNCaP cells were insensitive to TGF-beta 1 while, in others, they were sensitive to the growth inhibitory effect of TGF-beta 1. The present study was carried out to establish androgenic conditions that rendered LNCaP cells sensitive to TGF-beta 1. 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-beta 1 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-beta responsive promoter. Of the various DHT concentrations investigated in this study, these effects of TGF-beta 1 on LNCaP cells were consistently demonstrated only at 10(-10) M. At other concentrations, the effects of TGF-beta 1 were either minimal or undetectable. Accompanying these effects of TGF-beta 1, a low but statistically significant level of TGF-beta 1-specific binding and an increased protein level of TGF-beta 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-beta 1 and that DHT modulates the sensitivity to TGF-beta 1 and the level of TGF-beta receptor type II in these cells.
Kim
I Y
IY
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Zelner
D J
DJ
Sensibar
J A
JA
Ahn
H J
HJ
Park
L
L
Kim
J H
JH
Lee
C
C
D001667:Binding, Competitive; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D015533:Transcriptional Activation / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D013196:Dihydrotestosterone; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II