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Targeting gene transcription: a new strategy to down-regulate c-erbB-2 expression in mammary carcinoma.

Abstract：

:Overexpression of the c-erbB-2 proto-oncogene in mammary carcinoma is frequently associated with amplification of the c-erbB-2 gene, but it also occurs from single-copy gene. Studies in mammary-derived cell lines have shown that, whether or not the gene is amplified, there is a 6- to 8-fold increase in the accumulation of c-erbB-2 mRNA per gene copy in overexpressing cells. We have recently shown that this phenomenon is due to increased activity of the c-erbB-2 promoter mediated by the binding of a novel transcription factor, OB2-1, which is present at higher levels in overexpressing cells than in low expressors. OB2-1 activity therefore represents a novel therapeutic target for the down-regulation of c-erbB-2 levels in human cells. As a prototype for this strategy, we show here that the drug sodium aurothiomalate is able to inhibit the DNA-binding activity of OB2-1 in vitro and also to interfere with c-erbB-2 promoter activity in cell-based transfection assays. In addition, endogenous c-erbB-2 immunoreactivity was reduced in cells treated with aurothiomalate as compared with the levels observed in control cells.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Hollywood DP,Hurst HC

doi

10.1038/bjc.1995.146

subject

Has Abstract

pub_date

1995-04-01 00:00:00

pages

753-7

issue

4

eissn

0007-0920

issn

1532-1827

journal_volume

71

pub_type

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