Cisplatin induction of ERCC-1 mRNA expression in A2780/CP70 human ovarian cancer cells
Cisplatin induction of ERCC-1 mRNA expression in A2780/CP70 human ovarian cancer cells
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DOI：
10.1074/jbc.273.36.23419
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发表时间：
1998-09-04
影响因子：
4.8
通讯作者：
Reed, E
中科院分区：
文献类型：
--
作者：
Li, QD;Gardner, K;Reed, E
ERCC-1 is a critical gene within the nucleotide excision repair pathway, and cells without a functional ERCC-1 do not perform cisplatin-DNA adduct repair. We therefore investigated the cisplatin effect on ERCC-1 mRNA expression in vitro. In response to a l-h cisplatin exposure, A2780/CP70 human ovarian cancer cells showed a B-fold increase in steady-state level of ERCC-1 mRNA This rise was attributable to increased transcription as measured by nuclear run-on assays and a 60% increase in ERCC-1 mRNA half-life. The increase in ERCC-1 mRNA was preceded by a 4-5-fold rise in mRNA expressions of c-fos and c-jun, a 14-fold increase in c-Jun protein phosphorylation, and an increase in in vitro nuclear extract binding activity to the AP-1-like site of ERCC-1, These data suggest that the induction of ERCC-1 expression in A2780/CP70 cells exposed to cisplatin results from two major factors: (a) an increase in the expression of transactivating factors that bind the AP-1-like site in the 5'-flanking region of ERCC-1 and (b) an increase in the level of c-Jun phosphorylation that enhances its transactivation property.
