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Mol Carcinog. 2012 Jun;51(6):500-7. doi: 10.1002/mc.20813. Epub 2011 Jun 16.

Transcriptional down-regulation of Brca1 and E-cadherin by CtBP1 in breast cancer.

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  • 1Department of Dermatology, University of Colorado, Denver, Aurora, Colorado 80045, USA.

Abstract

Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor with oncogenic potential. Immunohistochemistry staining using human breast cancer tissue arrays revealed that 92% of invasive ductal breast cancer cases have CtBP1-positive staining compared to 4% CtBP1-positive in normal breast tissue. To explore the functional impact of CtBP1 in breast cancer, we examined CtBP1's transcriptional regulation of known tumor suppressors, breast cancer susceptibility gene 1 (Brca1), and E-cadherin. We found CtBP1 was recruited to the promoter regions of Brca1 and E-cadherin genes in breast cancer cells. Concomitantly, Brca1 loss was detected in 57% and E-cadherin loss was detected in 76% of human invasive ductal breast cancers, and correlated with CtBP1 nuclear staining in these lesions. Importantly, siRNA knock down of CtBP1 restored Brca1 and E-cadherin expression in breast cancer cell lines, implying CtBP1 down-regulates Brca1 and E-cadherin genes in human breast cancer. This study provides evidence that although genetic loss of Brca1 and E-cadherin are infrequent in breast cancer, they are down-regulated at the transcriptional level by CtBP1 expression. Thus, CtBP1 activation could be a potential biomarker for breast cancer development.

Copyright © 2011 Wiley Periodicals, Inc.

PMID:
21681822
[PubMed - indexed for MEDLINE]
PMCID:
PMC3177013
Free PMC Article
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