TGF-β repression of Id2 induces apoptosis in gut epithelial cells

被引：39

作者：

Cao, Y. ^{[1
]}

Liu, X. ^{[1
]}

Zhang, W. ^{[1
]}

Deng, X. ^{[1
]}

Zhang, H. ^{[1
]}

Liu, Y. ^{[2
]}

Chen, L. ^{[2
]}

Thompson, E. A. ^{[2
]}

Townsend, C. M., Jr. ^{[3
]}

Ko, T. C. ^{[1
]}

机构：

[1] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Houston, TX 77030 USA

[2] Mayo Clin, Ctr Comprehens Canc, Jacksonville, FL 32224 USA

[3] Univ Texas Galveston, Med Branch, Dept Surg, Galveston, TX 77550 USA

来源：

ONCOGENE | 2009年 / 28卷 / 08期

关键词：

apoptosis; affymetrix oligonucleotide microarrays; inhibitor of differentiation; TranSignal Protein/DNA arrays; hypoxia-inducing factor; GROWTH-FACTOR-BETA; LOOP-HELIX PROTEINS; INDUCIBLE TRANSCRIPTION; FACTOR GENE; HYPOXIA; DIFFERENTIATION; EXPRESSION; PROLIFERATION; ID-1; COOPERATION;

D O I：

10.1038/onc.2008.456

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Transforming growth factor-beta (TGF-beta) regulates epithelial tissue homeostasis by activating processes that control cell cycle arrest, differentiation and apoptosis. Disruption of the TGF-beta signaling pathway often occurs in colorectal cancers. Earlier, we have shown that TGF-beta induces apoptosis through the transcription factor Smad3. Affymetrix oligonucleotide microarrays were used to identify TGF-beta/Smad3 target genes that regulate apoptosis in rat intestinal epithelial cells (RIE-1). We found that TGF-beta repressed the expression of the inhibitor of differentiation (Id) gene family. Knockdown of Id1 and Id2 gene expression induced apoptosis in RIE-1 cells, whereas overexpression of Id2 attenuated TGF-beta-induced apoptosis. TranSignal Protein/ DNA arrays were used to identify the hypoxia-inducing factor-1 (HIF-1) as a downstream target of TGF-beta. HIF-1 is a basic helix-loop-helix protein, and overexpression of Id2 blocked HIF-1 activation by TGF-beta. Furthermore, knockdown of HIF-1 blocked TGF-beta-induced apoptosis. Thus, we have identified HIF-1 as a novel mediator downstream of Id2 in the pathway of TGF-beta-induced apoptosis.

引用

页码：1089 / 1098

页数：10

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