BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation

被引:67
作者
Logarajah, S
Hunter, P
Kraman, M
Steele, D
Lakhani, S
Bobrow, L
Venkitaraman, A
Wagner, S
机构
[1] Univ Cambridge, Dept Med, Wellcome Trust Immunol Unit, Cambridge CB2 2SP, England
[2] Inst Canc Res, Chester Beatty Labs, Breakthrough Toby Robbins Breast Canc Res Ctr, London SW3 6JB, England
[3] Univ Cambridge, Dept Pathol, Cambridge CB2 2XZ, England
[4] Univ Cambridge, Dept Oncol, Cambridge CB2 2XZ, England
[5] Univ Cambridge, MRC, Canc Cell Unit, Cambridge CB2 2XZ, England
[6] Univ Cambridge, Dept Haematol, Cambridge CB2 2XZ, England
基金
英国惠康基金;
关键词
mammary epithelium; differentiation; breast cancer; BCL-6; STAT;
D O I
10.1038/sj.onc.1206689
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
Appropriately timed proliferation, differentiation and apoptosis are essential to the normal functions of the mammary epithelium. Here, we report that the transcription factor BCL-6 is expressed in mammary epithelium in nonpregnant animals as well as during early pregnancy. When overexpressed in the nontransformed EpH4 mammary epithelial cell line, BCL-6 prevents the STAT-driven expression of the milk protein beta-casein and duct formation, and prevents apoptosis. Consistent with an antiapoptotic function, we demonstrate that BCL-6 is expressed in 68% of histologically high-grade ductal breast carcinomas, which are clinically the most aggressive. BCL-6 has previously been characterized as a regulator of B lymphocyte growth and development, but our work identifies a novel role for it in mammary epithelial differentiation, which may also implicate it in carcinogenesis.
引用
收藏
页码:5572 / 5578
页数:7
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