Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene
- PMID: 10675489
- DOI: 10.3892/ijo.16.3.555
Comparison of two human ovarian carcinoma cell lines (A2780/CP70 and MCAS) that are equally resistant to platinum, but differ at codon 118 of the ERCC1 gene
Abstract
ERCC1 is an essential gene within the nucleotide excision repair process. We studied two human ovarian carcinoma cell lines for cisplatin resistance, which differed with respect to ERCC1. The A2780/CP70 cell line has been extensively studied previously, and has the wild-type ERCC1 sequence. The MCAS cell line has a recently described ERCC1 polymorphism at codon 118, which is associated with an approximate 50% reduction in codon usage. These cells did not differ with respect to p53 sequence nor p53 mRNA induction following cisplatin exposure. The induction of ERCC1 mRNA was markedly reduced in MCAS cells as compared to A2780/CP70 cells. At the IC50 cisplatin dose for each cell line, MCAS cells were less proficient at cisplatin-DNA adduct repair than A2780/CP70 cells. In absolute terms, A2780/CP70 cells repaired 3-fold as much adduct (2.7 pg/microgram DNA over 6 h vs 0.86 pg/microgram DNA); and when expressed in terms of the maximal DNA adduct load, A2780/CP70 cells repaired 50% more adduct than MCAS cells. MCAS cells had increased cytosolic inactivation of drug at the IC50 dose level, which has been previously suggested to be a compensatory cellular response for reduced DNA repair capacity. These data suggest the possibility that this specific ERCC1 polymorphism, may be associated with reduced DNA repair capacity in human ovarian cancer cells. This association may be effected through a reduction in peak production of ERCC1 mRNA, and a consequent reduction in the translation of ERCC1 mRNA into protein.
Similar articles
-
Inhibition of Gli1 results in altered c-Jun activation, inhibition of cisplatin-induced upregulation of ERCC1, XPD and XRCC1, and inhibition of platinum-DNA adduct repair.Oncogene. 2012 Nov 1;31(44):4718-24. doi: 10.1038/onc.2011.610. Epub 2012 Jan 23. Oncogene. 2012. PMID: 22266871
-
In vitro studies on the mechanisms of oxaliplatin resistance.Cancer Chemother Pharmacol. 2001 Nov;48(5):398-406. doi: 10.1007/s002800100363. Cancer Chemother Pharmacol. 2001. PMID: 11761458
-
Absence of evidence for allelic loss or allelic gain for ERCC1 or for XPD in human ovarian cancer cells and tissues.Cancer Lett. 2000 Apr 14;151(2):127-32. doi: 10.1016/s0304-3835(99)00390-0. Cancer Lett. 2000. PMID: 10738106
-
Platinum-DNA adduct, nucleotide excision repair and platinum based anti-cancer chemotherapy.Cancer Treat Rev. 1998 Oct;24(5):331-44. doi: 10.1016/s0305-7372(98)90056-1. Cancer Treat Rev. 1998. PMID: 9861196 Review.
-
[ERCC1 as a Marker of Ovarian Cancer Resistance to Platinum Drugs].Antibiot Khimioter. 2015;60(3-4):42-50. Antibiot Khimioter. 2015. PMID: 26415382 Review. Russian.
Cited by
-
Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options.Biomed Res Int. 2016;2016:6896024. doi: 10.1155/2016/6896024. Epub 2016 Aug 1. Biomed Res Int. 2016. PMID: 27563673 Free PMC article. Review.
-
Single nucleotide polymorphisms and expression of ERCC1 and ERCC2 vis-à-vis chemotherapy drug cytotoxicity in human glioma.J Neurooncol. 2007 May;82(3):257-62. doi: 10.1007/s11060-006-9290-2. Epub 2006 Dec 7. J Neurooncol. 2007. PMID: 17151930
-
No evidence of an association of ERCC1 and ERCC2 polymorphisms with clinical outcomes of platinum-based chemotherapies in non-small cell lung cancer: a meta-analysis.Lung Cancer. 2011 Jun;72(3):370-7. doi: 10.1016/j.lungcan.2010.10.011. Epub 2010 Nov 13. Lung Cancer. 2011. PMID: 21075476 Free PMC article.
-
The ERCC1 N118N polymorphism does not change cellular ERCC1 protein expression or platinum sensitivity.Mutat Res. 2011 Mar 15;708(1-2):21-7. doi: 10.1016/j.mrfmmm.2011.01.002. Epub 2011 Feb 16. Mutat Res. 2011. PMID: 21315089 Free PMC article.
-
Polymorphisms of ERCC1 and XRCC1 predict the overall survival of advanced gastric cancer patients receiving oxaliplatin-based chemotherapy.Int J Clin Exp Med. 2015 Oct 15;8(10):18375-82. eCollection 2015. Int J Clin Exp Med. 2015. PMID: 26770441 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous