Autocrine TGF-β protects breast cancer cells from apoptosis through reduction of BH3-only protein, Bim

被引：48

作者：

Hoshino, Yukari ^{[1
]}

Katsuno, Yoko ^{[1
]}

Ehata, Shogo ^{[1
]}

Miyazono, Kohei ^{[1
]}

机构：

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

来源：

JOURNAL OF BIOCHEMISTRY | 2011年 / 149卷 / 01期

基金：

日本学术振兴会;

关键词：

TGF-beta; apoptosis; breast cancer; Bim; Foxc1; FORKHEAD/WINGED-HELIX GENE; MOUSE MAMMARY-CARCINOMA; DEPENDENT REGULATION; KINASE INHIBITOR; BONE METASTASIS; SMAD PATHWAYS; GROWTH; FOXC1; SURVIVAL; ACTIVATION;

D O I：

10.1093/jb/mvq114

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：

Cancer cells undergo multi-step processes in obtaining the ability to metastasize, and are constantly exposed to signals that induce apoptosis. Acquisition of anti-apoptotic properties by cancer cells is important for metastasis, and recent studies suggest that transforming growth factor (TGF)-beta promotes the survival of certain types of cancer cells. Here, we found that in highly metastatic breast cancer cells, JygMC(A), JygMC(B) and 4T1, TGF-beta ligands were produced in autocrine fashion. Pharmacological inhibition of endogenous TGF-beta signalling by a TGF-beta type I receptor kinase inhibitor in serum-free conditions increased the expression of BH3-only protein, Bim (also known as Bcl2-like 11) in JygMC(A) and JygMC(B) cells, and caused apoptotic cell death. We also found that induction of Bim by TGF-beta was not observed in Foxc1 knocked-down cancer cells. These findings suggest that TGF-beta plays a crucial role in the regulation of survival of certain types of cancer cells through the TGF-beta-Foxc1-Bim pathway, and that specific inhibitors of TGF-beta signalling might be useful as apoptosis inducers in breast cancer cells.

引用

页码：55 / 65

页数：11

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