Limits...
The CCAAT/enhancer-binding protein beta-2 isoform (CEBPβ-2) upregulates galectin-7 expression in human breast cancer cells.

Campion CG, Labrie M, Grosset AA, St-Pierre Y - PLoS ONE (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: INRS-Institut Armand-Frappier, Laval, Québec, Canada.

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.

Show MeSH

Related in: MedlinePlus

High C/EBPβ expression predicts poor outcome in human breast cancer.Data obtained from the Oncomine cancer microarray database (www.oncomine.org) showing higher C/EBPβ expression in (A) estrogen receptor (ER)-negative and (B) triple negative (TN) human breast carcinomas.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4008383&req=5

pone-0095087-g005: High C/EBPβ expression predicts poor outcome in human breast cancer.Data obtained from the Oncomine cancer microarray database (www.oncomine.org) showing higher C/EBPβ expression in (A) estrogen receptor (ER)-negative and (B) triple negative (TN) human breast carcinomas.

Mentions: To further examine whether we could find an association between C/EBPβ 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. We paid a particular attention to epithelial tissues known to express galectin-7 constitutively, including skin, esophagus, oral mucosa and cervical tissues. As expected, immunohistochemistry staining of normal epithelial tissues showed a predominantly nuclear pattern of C/EBPβ protein expression while galectin-7 was mostly found in the cytosolic and nuclear compartments (Figure 4). In all cases, the distribution of galectin-7 expression co-located with that of C/EBPβ. Identical findings were observed in normal mammary tissues where galectin-7 and C/EBPβ were both specifically expressed in myoepithelial cells. Using the ONCOMINE public cancer microarray database, we also found that C/EBPβ was expressed at significantly higher levels in oestrogen receptor (ER)-negative and triple-negative (TN) breast cancer tissues (Figure 5), a pattern identical to that of galectin-7 in human breast cancer tissues [9].


The CCAAT/enhancer-binding protein beta-2 isoform (CEBPβ-2) upregulates galectin-7 expression in human breast cancer cells.

Campion CG, Labrie M, Grosset AA, St-Pierre Y - PLoS ONE (2014)

High C/EBPβ expression predicts poor outcome in human breast cancer.Data obtained from the Oncomine cancer microarray database (www.oncomine.org) showing higher C/EBPβ expression in (A) estrogen receptor (ER)-negative and (B) triple negative (TN) human breast carcinomas.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4008383&req=5

pone-0095087-g005: High C/EBPβ expression predicts poor outcome in human breast cancer.Data obtained from the Oncomine cancer microarray database (www.oncomine.org) showing higher C/EBPβ expression in (A) estrogen receptor (ER)-negative and (B) triple negative (TN) human breast carcinomas.
Mentions: To further examine whether we could find an association between C/EBPβ 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. We paid a particular attention to epithelial tissues known to express galectin-7 constitutively, including skin, esophagus, oral mucosa and cervical tissues. As expected, immunohistochemistry staining of normal epithelial tissues showed a predominantly nuclear pattern of C/EBPβ protein expression while galectin-7 was mostly found in the cytosolic and nuclear compartments (Figure 4). In all cases, the distribution of galectin-7 expression co-located with that of C/EBPβ. Identical findings were observed in normal mammary tissues where galectin-7 and C/EBPβ were both specifically expressed in myoepithelial cells. Using the ONCOMINE public cancer microarray database, we also found that C/EBPβ was expressed at significantly higher levels in oestrogen receptor (ER)-negative and triple-negative (TN) breast cancer tissues (Figure 5), a pattern identical to that of galectin-7 in human breast cancer tissues [9].

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: INRS-Institut Armand-Frappier, Laval, Québec, Canada.

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.

Show MeSH
Related in: MedlinePlus