Smad7 mediates apoptosis induced by transforming growth factor β in prostatic carcinoma cells
Smad7 mediates apoptosis induced by transforming growth factor β in prostatic carcinoma cells
复制标题
DOI：
10.1016/s0960-9822(00)00470-x
复制
发表时间：
2000-05-04
期刊：
影响因子：
9.2
通讯作者：
Heldin, CH
中科院分区：
文献类型：
--
作者：
Landström, M;Heldin, NE;Heldin, CH
转化生长因子β (tgf - β)在某些细胞类型中是凋亡的重要调节因子，但其潜在的分子机制在很大程度上尚不清楚，tgf - β通过I型和II型受体以及下游效应蛋白Smads发出信号。tgf - β诱导Smad2和Smads（受体激活的Smads）磷酸化，Smad2和Smads与Smad4相关并转运到细胞核，在那里它们调节基因转录b[1]， Smad7蛋白由tgf - β 1诱导，并被归类为抑制性Smad。Smad7阻止受体激活的Smads磷酸化，从而抑制tgf - β诱导的信号反应[1]。Smad7在阉割后发生凋亡的大鼠前列腺上皮细胞中表达增加。本研究表明，tgf - β 1治疗或Smad7在人前列腺癌细胞（PC-3U）中的异位表达可诱导细胞凋亡。此外，tgf - β 1诱导的细胞凋亡可以通过抑制Smad7的表达、在稳定转染的细胞系中通过反义mRNA或在一些研究的细胞系中通过反义寡核苷酸瞬时转染来阻止。这些发现为Smad7在tgf - β 1信号传导中的新效应功能提供了证据。
Transforming growth factor beta (TGF-beta) is an important regulator of apoptosis in some cell types, but the underlying molecular mechanisms are largely unknown, TGF-beta signals through type I and type II receptors and downstream effector proteins, termed Smads. TGF-beta induces the phosphorylation of Smad2 and Smads (receptor-activated Smads) which associate with Smad4 and translocate to the nucleus, where they regulate gene transcription [1], Smad7 protein is induced by TGF-beta 1 and has been classified as an inhibitory Smad. Smad7 prevents phosphorylation of receptor-activated Smads, thereby inhibiting TGF-beta induced signaling responses [1]. Smad7 expression is increased in rat prostatic epithelial cells undergoing apoptosis as a result of castration [2]. Here we have shown that TGF-beta 1 treatment or ectopic expression of Smad7 in human prostatic carcinoma cells (PC-3U) induces apoptosis. Furthermore, TGF-beta 1-induced apoptosis was prevented by inhibition of Smad7 expression, by antisense mRNA in stably transfected cell lines or upon transient transfection with antisense oligonucleotides in several investigated cell lines. These findings provide evidence for a new effector function for Smad7 in TGF-beta 1 signaling.