Expression of the CCAAT/enhancer-binding proteins C/EBPα, C/EBPβ and C/EBPδ in breast cancer: correlations with clinicopathologic parameters and cell-cycle regulatory proteins

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SummaryMembers of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors are involved in the regulation of proliferation and differentiation of the mammary gland. In order to investigate the role of C/EBPα, -β and -δ in breast cancer, we performed western blot analysis and partly immunohistochemistry in 75 mammary carcinomas, 10 normal mammary tissue samples and four mammary cell lines. Expression levels of both C/EBPα isoforms, C/EBPβ isoforms LAP1, LAP2 (liver-enriched transcriptional activating proteins), and LIP (liver-enriched transcriptional inhibitory protein), and C/EBPδ in the tumors were correlated with clinicopathological tumor parameters, expression of estrogen and progesterone receptors (ER, PR), Ki67 immunostaining, and expression of seven cell-cycle regulatory proteins which had been analyzed before. High C/EBPα and -δ protein levels correlated significantly with expression of cell-cycle promoters (cyclin D1 and E) and cell-cycle inhibitory proteins (Rb, p27, p16), but with none of the established prognostic parameters. In contrast, statistically significant relationships of the full-length C/EBPβ isoform LAP1 and a negative estrogen receptor status, high grading, nodal involvement, and high cyclin E and p16 expression were found. For the shorter isoform LIP, correlations with an ER-negative phenotype and high Ki67 immunostaining were detected, and high histological grading (G3) correlated with lower LAP/LIP ratio. These results suggest that high C/EBPβ expression might be involved in tumor progression and indicative of an unfavorable prognosis.

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