کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2146684 1548365 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The ERCC1 N118N polymorphism does not change cellular ERCC1 protein expression or platinum sensitivity
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
The ERCC1 N118N polymorphism does not change cellular ERCC1 protein expression or platinum sensitivity
چکیده انگلیسی

Genetic polymorphisms in ERCC1 are thought to contribute to altered sensitivity to platinum-based chemotherapy. Although ERCC1 N118N (500 C>T, rs11615) is the most studied polymorphism, the impact of this polymorphism on platinum-based chemotherapy remains unclear. This is the first study in which the functional impact of ERCC1 N118N on gene expression and platinum sensitivity was explored. The aim of this study is to investigate if the reduced codon usage frequency of AAT, which contains the variant allele of the silent mutation, has functional impact on ERCC1 in a well-controlled biological system. Specifically, the ERCC1 cDNA clone with either the C or T allele was introduced into an ERCC1 deficient cell line, UV20, and assayed for the effect of the two alleles on ERCC1 transcription, translation and platinum sensitivity. Both ERCC1 mRNA and protein expression levels increased upon cisplatin treatment, peaking at 4 h post-treatment, however there were no differences between the two alleles (p > 0.05). Cells complemented with ERCC1 showed significantly higher survival proportion than the parental cell line following platinum exposure (p < 0.0001), although no differences were observed between the cells transfected with the wild type or the polymorphic allele. These data suggest that N118N itself is not related to the phenotypic differences in ERCC1 expression or function, but rather this polymorphism may be linked to other causative variants or haplotypes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis - Volume 708, Issues 1–2, 15 March 2011, Pages 21–27
نویسندگان
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