Regulation of apoptosis induced by transforming growth factor-beta1 in nontumorigenic rat prostatic epithelial cell lines.
Transforming growth factor-beta1 (TGF-beta1), which is induced in the prostate following castration, has been speculated to mediate apoptosis of epithelial cells during prostatic involution. Here, we report the first evidence of a direct effect of TGF-beta on induction of apoptosis in prostatic epithelial cells in vitro, using NRP-152 nontumorigenic and NRP-154 tumorigenic rat prostatic epithelial cell lines. TGF-beta1 induces apoptosis of both cell lines within 24 h, as shown by a decrease in cell viability, in situ DNA nick-end labeling, and internucleosomal DNA fragmentation. Moreover, the ability of TGF-beta to induce apoptosis of NRP-152 is strictly dependent on culture conditions, because dexamethasone enhances while insulin and insulin-like growth factor-I specifically block apoptosis induced by TGF-beta. We suggest that TGF-betas are direct physiological regulators of apoptosis of prostatic epithelial cells.
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892, USA.
A Y
AY
Hsing
K
K
Kadomatsu
M J
MJ
Bonham
D
D
Danielpour
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008297:Male; D009707:Nucleosomes; D011467:Prostate / Q000503:physiopathology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D005938:Glucocorticoids; D007328:Insulin; D009707:Nucleosomes; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone