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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Breast Neoplasms / chemistry*
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Breast Neoplasms / etiology
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Cell Differentiation
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Cell Division
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Epithelial Cells / cytology
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Female
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Humans
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Mammary Glands, Animal / cytology*
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Mice
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Milk Proteins*
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Proto-Oncogene Proteins / analysis
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-bcl-6
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RNA, Messenger / analysis
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STAT5 Transcription Factor
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Trans-Activators / metabolism
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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DNA-Binding Proteins
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Milk Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-6
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RNA, Messenger
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STAT5 Transcription Factor
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Trans-Activators
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Transcription Factors