Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04155 (
pS2
)
1,234
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cofactor of BRCA1 (COBRA1) is a newly characterized member of the negative elongation factor (NELF) complex. In this work, we show that COBRA1 is overexpressed in the majority of primary upper gastrointestinal adenocarcinomas (UGC), and its overexpression correlates with down-regulation of
TFF1
. We have detected overexpression of COBRA1 mRNA using quantitative real-time reverse transcription-PCR in 28 (79%) primary UGCs. Immunohistochemical analysis of UGC tissue arrays that contained 70 tumor samples showed moderate-strong staining for COBRA1 in 60 (84%) tumors. Interestingly, the tumor samples showed absent-weak staining for
TFF1
in 45 (65%) of the tumors. Simultaneous loss of
TFF1
expression and overexpression of COBRA1 was observed in 42 of 70 (60%) tumors. Using small interfering RNA technology with gastric cancer cells, we have shown that COBRA1 inhibition leads to increased
TFF1
promoter activity and gene expression. Promoter analysis of
TFF1
indicated that regulation of
TFF1
by COBRA1 is estrogen independent in contrast to breast cancer. Moreover, COBRA1 regulation of
TFF1
in gastric cancer cells was independent of
NELF-E
. Using several truncated mutants and site mutants of the
TFF1
promoter, we have shown that COBRA1 can negatively regulate the activator protein-1 (AP-1) complex at the
TFF1
promoter and thus down-regulate
TFF1
expression in gastric cancer cell lines. Electrophoretic mobility shift assay showed that COBRA1 attenuates AP-1 binding to DNA. Our results suggest COBRA1 as a novel oncogene in UGCs that regulate AP-1 binding and the expression of
TFF1
in upper gastric epithelia.
...
PMID:Cofactor of BRCA1: a novel transcription factor regulator in upper gastrointestinal adenocarcinomas. 1645 88
