The CCAAT/enhancer-binding protein beta-2 isoform (CEBPβ-2) upregulates galectin-7 expression in human breast cancer cells.
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/EBPβ) 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/EBPβ-2 (also known as LAP2), the most transcriptionally active of the C/EBPβ isoforms. Our results showed that ectopic expression of C/EBPβ-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/EBPβ-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/EBPβ 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/EBPβ 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.
INRS-Institut Armand-Frappier, Laval, Québec, Canada.
Carole G
CG
Campion
INRS-Institut Armand-Frappier, Laval, Québec, Canada.
Marilyne
M
Labrie
INRS-Institut Armand-Frappier, Laval, Québec, Canada.
Andrée-Anne
AA
Grosset
INRS-Institut Armand-Frappier, Laval, Québec, Canada.
Yves
Y
St-Pierre
D001483:Base Sequence; D001943:Breast Neoplasms / Q000473:pathology*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D045744:Cell Line, Tumor; D016384:Consensus Sequence / Q000235:genetics; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D037161:Galectins / Q000235:genetics*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D015854:Up-Regulation
D022782:CCAAT-Enhancer-Binding Protein-beta; D037161:Galectins; C092525:LGALS7 protein, human