Down-regulation end growth inhibitory role of C/EBPα in breast cancer

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/EBP alpha is involved in breast cancer. Experimental Design: We quantified C/EBP alpha 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/EBP alpha protein levels were further determined by immunohistochemical analysis. To examine the consequence of C/EPB alpha expression in breast cancer, we stably transfected an inducible C/EPB alpha expression vector into three breast cancer cell lines. Results: Low expression of C/EBP alpha mRNA was found in 83% of primary breast cancer samples. Immunohistochemical study further showed either a markedly reduced or undetectable expression of C/EBP alpha protein in 30% of breast cancer specimens. The other 70% of breast cancers had C/EBP alpha expression in both the cytoplasm and nucleus; in control, C/EBP alpha was localized to the nucleus in the normal ductal cells. C/EBP alpha expression was associated with estrogen- and progesterone receptor-negative status. Induction of C/EBP alpha expression in these cell lines resulted in growth inhibition accompanied by G(0)-G(1) cell cycle arrest and reduced anchorage-independent cell growth. C/EBP alpha expression was associated with down-regulation of c-myc and up-regulation of p21, PPAR gamma, and the breast epithelial differentiation marker, maspin. Conclusions: These results suggest that reduced expression of C/EBPa may play a role in the development and/or progression of breast cancer.