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Expression of Galectin-7 Is Induced in Breast Cancer Cells by Mutant p53

Campion, Carole G.; Labrie, Marilyne; Lavoie, Geneviève; St-Pierre, Yves (2013). Expression of Galectin-7 Is Induced in Breast Cancer Cells by Mutant p53 PLoS ONE , vol. 8 , nº 8. e72468. DOI: 10.1371/journal.pone.0072468.

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Résumé

Galectin-7 was initially described as a marker of epithelial differentiation expressed in the stratified epithelium of various tissues. Like other members of the galectin family, its expression level is often significantly altered in cancer cells. In breast cancer, its expression is significantly augmented in aggressive molecular subtypes, most notably in estrogen receptor-negative tumors and in cell lines with a basal-like phenotype. Studies using experimental mouse models have further shown high expression of galectin-7 was sufficient to increase the metastatic behavior of poorly metastatic breast cancer cells, rendering them more resistant to apoptosis. This expression pattern in breast cancer cells is unexpected because galectin-7 was originally identified as a p53-induced gene. To address this paradox, we have examined the molecular mechanisms regulating galectin-7 in breast cancer cells. Our results showed that transfection of breast cancer cells with expression vectors encoding mutant p53 was sufficient to induce galectin-7 at both mRNA and protein levels. Doxorubicin treatment of breast cancer cells harboring a mutant p53 also induced galectin-7. This induction was specific since knockdown of endogenous mutant p53 inhibited doxorubicin-induced galectin-7 expression. The p53-induced galectin-7 expression in breast cancer cells correlated with increased NF-kappaB activity and was inhibited by NF-kappaB inhibitors, indicating that the ability of mutant p53 to induce galectin-7 was dependent on NF-kappaB activity. The implication of NF-kappaB was further supported by data showing that NF-kappaB bound to the endogenous galectin-7 promoter and that TNFalpha-induced galectin-7 expression was abolished by NF-kappaB inhibitors. Taken together, our data provide an explanation to the observed high galectin-7 expression levels in cancer cells and suggest that galectin-7 could be part of a common pathway used by mutant p53 to promote cancer progression.

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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 19 juin 2017 20:02
Dernière modification: 19 juin 2017 20:02
URI: http://espace.inrs.ca/id/eprint/2871

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