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转化生长因子-β1诱导的非致瘤性大鼠前列腺上皮细胞系凋亡的调控

Regulation of apoptosis induced by transforming growth factor-beta1 in nontumorigenic rat prostatic epithelial cell lines.

作者信息

Hsing A Y, Kadomatsu K, Bonham M J, Danielpour D

机构信息

Laboratory of Chemoprevention, National Cancer Institute, Bethesda, Maryland 20892, USA.

出版信息

Cancer Res. 1996 Nov 15;56(22):5146-9.

PMID:8912849
Abstract

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.

摘要

去势后前列腺中诱导产生的转化生长因子-β1(TGF-β1)被推测在前列腺退化过程中介导上皮细胞凋亡。在此,我们利用NRP - 152非致瘤性和NRP - 154致瘤性大鼠前列腺上皮细胞系,首次报道了TGF-β对体外前列腺上皮细胞凋亡诱导的直接作用的证据。TGF-β1在24小时内诱导两种细胞系凋亡,表现为细胞活力下降、原位DNA缺口末端标记和核小体间DNA片段化。此外,TGF-β诱导NRP - 152凋亡的能力严格依赖于培养条件,因为地塞米松增强而胰岛素和胰岛素样生长因子-I特异性阻断TGF-β诱导的凋亡。我们认为TGF-β是前列腺上皮细胞凋亡的直接生理调节因子。

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