Knockdown of BCL2L12 leads to cisplatin resistance in MDA-MB-231 breast cancer cells

被引：34

作者：

Hong, Yi ^{[1
]}

Yang, Junwu ^{[1
]}

Wu, Weibing ^{[1
]}

Wang, Wenzong ^{[1
]}

Kong, Xiangfei ^{[1
]}

Wang, Yanlin ^{[1
]}

Yun, Xiaojing ^{[1
]}

Zong, Hongliang ^{[1
]}

Wei, Yuanyan ^{[1
]}

Zhang, Si ^{[1
]}

Gu, Jianxing ^{[1
]}

机构：

[1] Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Ctr Gene Res, Shanghai 200032, Peoples R China

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2008年 / 1782卷 / 11期

关键词：

Apoptosis; Breast cancer; BCL2L12; Cisplatin; beta-Catenin; MDA-MB-231; MCF-7;

D O I：

10.1016/j.bbadis.2008.09.008

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：

BCL2L12, a newly identified member of Bcl-2 family. contains a BH2 domain and a putative BH3 domain. It was found to be highly expressed in normal breast tissues, and was associated with favorable prognosis in breast cancer patients. Here, we reported that the mRNA levels of BCL2L12 and its transcript variant BCL2L12A could be upregulated upon cisplatin treatment in MDA-MB-231 breast cancer cells. Knockdown of BCL2L12 and BCL2L12A dramatically inhibited cisplatin-induced apoptosis. In contrast, ectopic expressions of each of the proteins promoted cisplatin-induced apoptosis. These results indicated that decreased expressions or loss of BCL2L12 and BCL2L12A may contribute to the cisplatin resistance in breast cancer patients. Furthermore, we found that cisplatin-induced downregulation of beta-catenin was partially suppressed in BCL2L12- and B3CL2L12A-knocked down MDA-MB-231 cells, which indicated that knockdown of these two proteins may stabilize beta-catenin in cisplatin-induced apoptosis. In short, we proposed that BCL2L12 and BCL2L12A may play an important role in cisplatin-induced apoptosis in MDA-MB-231 breast cancer cells. Crown Copyright (c) 2008 Published by Elsevier B.V. All rights reserved.

引用

页码：649 / 657

页数：9

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