Abstract
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.
Highlights
Galectins constitute a family of lectins defined by shared consensus amino acid sequences and affinity for b-galactosecontaining oligosaccharides [1]
Expression of galectin-7 and C\EBPb in epithelial tissues To further examine whether we could find an association between C/EBPb and galectin-7 expression profiles in epithelial tissues, we looked at the Human Protein Atlas database, which contains high-resolution images showing the spatial distribution of proteins in normal and cancer tissues
There is an increasing number of reports, showing that galectin-7 is overly expressed in cancer cells, most notably in as esophageal, lung and buccal squamous cell carcinomas, thyroid carcinomas, bladder cancer, lymphoma, and breast cancer [7,20,21,22,23,24,25]
Summary
Galectins constitute a family of lectins defined by shared consensus amino acid sequences and affinity for b-galactosecontaining oligosaccharides [1]. The distribution of galectins is tissue-specific and their expression is developmentally regulated [1,2] They play an important role in several physiological processes, including embryonic development, wound healing, apoptosis, intercellular adhesion, cell migration, and immune response. They are involved in a number of pathological conditions, including infectious diseases and cancer. Galectin-7 remains an unfamiliar member of the galectin family. This galectin was initially described as a marker of differentiation of stratified epithelia by Magnaldo and colleagues [3]. Galectin-7 has been considered an apoptosis regulator in many cell systems since its discovery by the group of Bert Vogelstein as one of the 14 transcripts out of 7,202 induced in colorectal cancer cells by the expression of p53, whose major function is to control apoptosis [5]
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