BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation.
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.
Logarajah
Suresh
S
Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Cambridge, CB2 2SP, UK.
Hunter
Patricia
P
Kraman
Matthew
M
Steele
Dawn
D
Lakhani
Sunil
S
Bobrow
Lynda
L
Venkitaraman
Ashok
A
Wagner
Simon
S
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000209:etiology; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology*; D051379:Mice; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000032:analysis; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors