The CCAAT/Enhancer-Binding Protein Beta-2 Isoform (CEBPbeta-2) Upregulates Galectin-7 Expression in Human Breast Cancer Cells

Campion, Carole G.; Labrie, Marilyne; Grosset, Andrée-Anne et St-Pierre, Yves (2014). The CCAAT/Enhancer-Binding Protein Beta-2 Isoform (CEBPbeta-2) Upregulates Galectin-7 Expression in Human Breast Cancer Cells PLoS ONE , vol. 9 , nº 5. e95087. DOI: 10.1371/journal.pone.0095087.

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Résumé

Galectin-7 is considered a gene under the control of p53. However, elevated expression of galectin-7 has been reported in several forms of cancer harboring an inactive p53 pathway. This is especially true for breast cancer where galectin-7 expression is readily expressed in a high proportion in basal-like breast cancer tissues, conferring cancer cells with increased resistance to cell death and metastatic properties. These observations suggest that other transcription factors are capable of inducing galectin-7 expression. In the present work, we have examined the role of CCAAT/enhancer-binding protein beta (C/EBPbeta) in inducing expression of galectin-7. C/EBP proteins have been shown to contribute to breast cancer by upregulating pro-metastatic genes. We paid particular attention to C/EBPbeta-2 (also known as LAP2), the most transcriptionally active of the C/EBPbeta isoforms. Our results showed that ectopic expression of C/EBPbeta-2 in human breast cancer cells was sufficient to induce expression of galectin-7 at both the mRNA and protein levels. In silico analysis further revealed the presence of an established CEBP element in the galectin-7 promoter. Mutation of this binding site abolished the transcriptional activity of the galectin-7 promoter. Chromatin immunoprecipitation analysis confirmed that C/EBPbeta-2 binds to the endogenous galectin-7 promoter. Analysis of galectin-7 protein expression in normal epithelia and in breast carcinoma by immunohistochemistry further showed the expression pattern of C/EBPbeta closely micmicked that of galectin-7, most notably in mammary myoepithelial cells and basal-like breast cancer where galectin-7 is preferentially expressed. Taken together, our findings suggest that C/EBPbeta is an important mediator of galectin-7 gene activation in breast cancer cells and highlight the different transcriptional mechanisms controlling galectin-7 in cancer cells.

Type de document:	Article
Mots-clés libres:	-
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	09 mars 2016 15:18
Dernière modification:	09 mars 2016 15:18
URI:	https://espace.inrs.ca/id/eprint/3015

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