Expression of the CCAAT/enhancer-binding proteins C/EBPalpha, C/EBPbeta and C/EBPdelta in breast cancer: correlations with clinicopathologic parameters and cell-cycle regulatory proteins.
Members 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/EBPalpha, -beta and -delta 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/EBPalpha isoforms, C/EBPbeta isoforms LAP1, LAP2 (liver-enriched transcriptional activating proteins), and LIP (liver-enriched transcriptional inhibitory protein), and C/EBPdelta 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/EBPalpha and -delta 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/EBPbeta 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/EBPbeta expression might be involved in tumor progression and indicative of an unfavorable prognosis.
Milde-Langosch
Karin
K
Institute of Pathology, Department of Gynecopathology, University-Hospital Hamburg-Eppendorf (UKE), Hamburg, Germany. milde@uke.uni-hamburg.de
Löning
Thomas
T
Bamberger
Ana-Maria
AM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000235:genetics / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D016009:Chi-Square Distribution; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000235:genetics; D013223:Statistics as Topic; D014157:Transcription Factors
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; D020033:Protein Isoforms; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta