A role for Id in the regulation of TGF-β-induced epithelial-mesenchymal transdifferentiation

被引：121

作者：

Kondo, M

Cubillo, E

Tobiume, K

Shirakihara, T

Fukuda, N

Suzuki, H

Shimizu, K

Takehara, K

Cano, A

Saitoh, M

Miyazono, K

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Bunkyo Ku, Tokyo 1130033, Japan

[2] Kanazawa Univ, Grad Sch Med Sci, Dept Dermatol, Sch Med, Kanazawa, Ishikawa 9208641, Japan

[3] JFCR, Inst Canc, Dept Biochem, Toshima Ku, Tokyo 1708455, Japan

[4] CSIC, UAM, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain

[5] UAM, Dept Bioquim, Madrid 28029, Spain

[6] Nippon Med Coll, Grad Sch Med, Inst Dev & Aging Sci, Dept Mol Oncol,Nakahara Ku, Kanagawa 2118533, Japan

[7] Kirin Brewery Co Ltd, Pharmaceut Res Lab, Gunma 3701295, Japan

来源：

CELL DEATH AND DIFFERENTIATION | 2004年 / 11卷 / 10期

关键词：

TGF-beta; epithelial-mesenchymal transdifferentiation; Id; E2A; helix-loop-helix factors;

D O I：

10.1038/sj.cdd.4401467

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：

Epithelial-mesenchymal transdifferentiation (EMT) is a critical morphogenic event that occurs during embryonic development and during the progression of various epithelial tumors. EMT can be induced by transforming growth factor (TGF)-beta in mouse NMuMG mammary epithelial cells. Here, we demonstrate a central role of helix-loop-helix factors, E2A and inhibitor of differentiation (Id) proteins, in TGF-beta-induced EMT. Epithelial cells ectopically expressing E2A adopt a fibroblastic phenotype and acquire migratory/invasive properties, concomitant with the suppression of E-cadherin expression. Id proteins interacted with E2A proteins and antagonized E2A-dependent suppression of the E-cadherin promoter. Levels of Id proteins were dramatically decreased by TGF-beta. Moreover, NMuMG cells overexpressed Id2 showed partial resistance to TGF-beta-induced EMT. Id proteins thus inhibit the action of E2A proteins on the expression of E-cadherin, but after TGF-beta stimulation, E2A proteins are present in molar excess of the Id proteins, thus over-riding their inhibitory function and leading to EMT.

引用

页码：1092 / 1101

页数：10

共 46 条

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