Growth inhibitory signalling by TGFbeta is blocked in Ras-transformed intestinal epithelial cells at a post-receptor locus.
Growth inhibitory signalling by TGFbeta is blocked in Ras-transformed intestinal epithelial cells at a post-receptor locus.
复制标题
Ras 转化的肠上皮细胞中 TGFbeta 的生长抑制信号在受体后位点被阻断。
DOI:
10.1016/s0898-6568(03)00010-x
复制
发表时间:
2003
影响因子:
4.8
通讯作者:
Barnard,John
中科院分区:
文献类型:
--
作者:
Jiang,Bo;Zhang,Jin-San;Du,Jianguo;Urrutia,Raul;Barnard,John
The transforming growth factor β (TGFβ) family of growth regulatory peptides plays an important role in the regulation of gastrointestinal epithelial cell homeostasis. Loss of growth inhibitory signalling by TGFβ is common in the context of Ras-transformation and it has been hypothesized that loss of TGFβ receptor II (TGFβRII) expression accounts for the emergence of TGFβ resistance. Here we examine the functional significance of reduced TGFβRII expression in intestinal epithelial cells transformed by oncogenic Ras. TGFβ-induced signalling events downstream of TGFβRII were examined in Ras-transformed RIE-1 cells (RIE-Ras) and compared to the parental RIE-1 line. RIE-Ras cells were resistant to growth inhibition by TGFβ. Neither overexpression of TGFβRII in RIE-Ras cells nor expression of constitutively active TGFβRI restored sensitivity to TGFβ. TGFβ-mediated phosphorylation of Smad2 occurred in TGFβ-resistant RIE-Ras cells, as well as other TGFβ-resistant cells lines (HT-29, SW620) expressing low levels of TGFβRII. Nuclear translocation of Smad2 and Smad4 occurred equally in RIE-Ras and parental RIE cells. The activity of TIEG2, a TGFβ-inducible SP1-like transcription factor, was reduced in RIE-Ras cells, implying that resistance in Ras-transformed RIE cells occurs by a transcriptional mechanism.
登录
查看更多内容
DOI:
--
发表时间:
1988
期刊:
影响因子:
--
作者:
A. Stalcup;D. Martire;S. Wise
通讯作者:
S. Wise
影响因子:
4.1
作者:
K. Jinno;T. Nagoshi;N. Tanaka;M. Okamoto;J. Fetzer;W. R. Biggs
通讯作者:
W. R. Biggs
DOI:
--
发表时间:
1987
期刊:
影响因子:
--
作者:
Pankaj Shah;L. Rogers;J. Fetzer
通讯作者:
J. Fetzer
DOI:
--
发表时间:
1986
期刊:
影响因子:
--
作者:
P. Zhu
通讯作者:
P. Zhu
影响因子:
1.7
作者:
A. M. Krstulović;H. Colin;A. Tchapla;G. Guiochon
通讯作者:
G. Guiochon