کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2114072 1084515 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fanconi Anemia pathway heterogeneity revealed by cisplatin and oxaliplatin treatments
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Fanconi Anemia pathway heterogeneity revealed by cisplatin and oxaliplatin treatments
چکیده انگلیسی

Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents. However, the cytotoxicity of other commonly used cancer therapeutics in cells with FA pathway defects remains to be defined. Here, we focused on the effects of cisplatin and oxaliplatin in a panel of HNSCC and fibroblast cell lines. We found that FANCC- and FANCD2-mutant cells were unexpectedly more sensitive to platinum drugs than FANCA-mutant cells, and mono-ubiquitination of FANCD2, which is mediated by the FANCA and FANCC containing FA core complex was not required for platinum resistance. Interestingly, platinum hypersensitivity could be dissociated from mitomycin C hypersensitivity suggesting different underlying mechanisms. FANCD2 or RAD51 subnuclear foci were not useful as biomarkers of platinum hypersensitivity of FANCC/FANCD2-mutant cells. Our data add to an emerging body of evidence indicating that the FA pathway is not linear and that several protein subcomplexes with different functions exist. It will be important to establish biomarkers that can predict the sensitivity of tumors with specific FA defects to chemotherapeutic agents.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 292, Issue 1, 1 June 2010, Pages 73–79
نویسندگان
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