Document Detail

Modulation of excision repair cross complementation group 1 (ERCC-1) mRNA expression by pharmacological agents in human ovarian carcinoma cells.
MedLine Citation:
PMID:  9933022     Owner:  NLM     Status:  MEDLINE    
Excision repair cross complementation group 1 (ERCC-1) is a DNA repair gene that is essential for life, and it appears to be a marker gene for nucleotide excision repair activity. Overexpression of ERCC-1 during cisplatin-based chemotherapy is associated with clinical and cellular drug resistance. We therefore began to assess the influence of various pharmacological agents on the induction of ERCC-1 mRNA in A2780/CP70 human ovarian carcinoma cells. Cisplatin exposure in culture resulted in a 4- to 6-fold induction for the steady-state level of ERCC-1 mRNA in A2780/CP70 cells. ERCC-1 mRNA induction was concentration and time dependent. Cyclosporin A and herbimycin A, which suppress c-fos and c-jun gene expressions, respectively, blocked the cisplatin-induced increase in ERCC-1 mRNA. This effect of cyclosporin A or herbimycin A on the down-regulation of ERCC-1 correlates with enhanced cytotoxicity of cisplatin in this system. The products of c-fos and c-jun are components of the transcription factor AP-1 (activator protein 1). 12-O-Tetradecanoylphorbol 13-acetate (TPA), a known AP-1 agonist, induced ERCC-1 mRNA to the same extent as cisplatin, but did not synergize with cisplatin in this regard. The TPA effect was biphasic, with an initial increase during the first 1-6 hr, followed by decreasing mRNA levels at 24-72 hr. These data suggest that the effects of these pharmacological agents on ERCC-1 gene expression may be mediated through the modulation of AP-1 activities.
Q Li; B Tsang; F Bostick-Bruton; E Reed
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  57     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-02-10     Completed Date:  1999-02-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  347-53     Citation Subset:  IM    
Medical Ovarian Cancer Section, Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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MeSH Terms
Cisplatin / pharmacology*
Cyclosporine / pharmacology
DNA Repair*
DNA-Binding Proteins*
Gene Expression Regulation / drug effects*
Lactams, Macrocyclic
Protein Biosynthesis
Proteins / genetics*
Quinones / pharmacology
RNA, Messenger / biosynthesis
Tetradecanoylphorbol Acetate / pharmacology
Tumor Cells, Cultured
Reg. No./Substance:
0/Benzoquinones; 0/DNA-Binding Proteins; 0/Lactams, Macrocyclic; 0/Proteins; 0/Quinones; 0/RNA, Messenger; 15663-27-1/Cisplatin; 16561-29-8/Tetradecanoylphorbol Acetate; 59865-13-3/Cyclosporine; 70563-58-5/herbimycin; EC 3.1.-/ERCC1 protein, human; EC 3.1.-/Endonucleases

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