title: Transcriptional down-regulation of Brca1 and E-cadherin by CtBP1 in breast cancer.
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.
authors.affiliation: Department of Dermatology, University of Colorado, Denver, Aurora, Colorado 80045, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Gangwen
authors.initials: G
authors.lastname: Han
authors.forename: Stephen
authors.initials: S
authors.lastname: Malkoski
authors.forename: Bolin
authors.initials: B
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D019313:BRCA1 Protein / Q000235:genetics*; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D019313:BRCA1 Protein; D015820:Cadherins; D004268:DNA-Binding Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein