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  • Title: Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer.
    Author: Gery S, Tanosaki S, Bose S, Bose N, Vadgama J, Koeffler HP.
    Journal: Clin Cancer Res; 2005 May 01; 11(9):3184-90. PubMed ID: 15867211.
    Abstract:
    PURPOSE: CCAAT/enhancer binding proteins (C/EBP) are a family of transcription factors that regulate proliferation and differentiation in a variety of tissues. The purpose of this study was to explore the possibility that C/EBPalpha is involved in breast cancer. EXPERIMENTAL DESIGN: We quantified C/EBPalpha mRNA expression levels in 24 primary breast tumors, 16 normal breast samples, and 8 breast cancer cell lines using quantitative real-time reverse transcription-PCR assay. C/EBPalpha protein levels were further determined by immunohistochemical analysis. To examine the consequence of C/EPBalpha expression in breast cancer, we stably transfected an inducible C/EPBalpha expression vector into three breast cancer cell lines. RESULTS: Low expression of C/EBPalpha mRNA was found in 83% of primary breast cancer samples. Immunohistochemical study further showed either a markedly reduced or undetectable expression of C/EBPalpha protein in 30% of breast cancer specimens. The other 70% of breast cancers had C/EBPalpha expression in both the cytoplasm and nucleus; in control, C/EBPalpha was localized to the nucleus in the normal ductal cells. C/EBPalpha expression was associated with estrogen- and progesterone receptor-negative status. Induction of C/EBPalpha expression in these cell lines resulted in growth inhibition accompanied by G0-G1 cell cycle arrest and reduced anchorage-independent cell growth. C/EBPalpha expression was associated with down-regulation of c-myc and up-regulation of p21, PPARgamma, and the breast epithelial differentiation marker, maspin. CONCLUSIONS: These results suggest that reduced expression of C/EBPalpha may play a role in the development and/or progression of breast cancer.
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