title: BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation.
abstract: 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.
authors.affiliation: Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Cambridge, CB2 2SP, UK.
authors.forename: Suresh
authors.initials: S
authors.lastname: Logarajah
authors.forename: Patricia
authors.initials: P
authors.lastname: Hunter
authors.forename: Matthew
authors.initials: M
authors.lastname: Kraman
authors.forename: Dawn
authors.initials: D
authors.lastname: Steele
authors.forename: Sunil
authors.initials: S
authors.lastname: Lakhani
authors.forename: Lynda
authors.initials: L
authors.lastname: Bobrow
authors.forename: Ashok
authors.initials: A
authors.lastname: Venkitaraman
authors.forename: Simon
authors.initials: S
authors.lastname: Wagner
mesh_terms: 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*
chemical_list: 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