Literature DB >> 15867211

Down-regulation and growth inhibitory role of C/EBPalpha in breast cancer.

Sigal Gery1, Sakae Tanosaki, Shikha Bose, Namrata Bose, Jay Vadgama, H Phillip Koeffler.   

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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Year:  2005        PMID: 15867211     DOI: 10.1158/1078-0432.CCR-04-2625

Source DB:  PubMed          Journal:  Clin Cancer Res        ISSN: 1078-0432            Impact factor:   12.531


  36 in total

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9.  Role of WISP-2/CCN5 in the maintenance of a differentiated and noninvasive phenotype in human breast cancer cells.

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10.  C/EBPalpha expression is partially regulated by C/EBPbeta in response to DNA damage and C/EBPalpha-deficient fibroblasts display an impaired G1 checkpoint.

Authors:  R Ranjan; E A Thompson; K Yoon; R C Smart
Journal:  Oncogene       Date:  2009-07-06       Impact factor: 9.867

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