کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2151955 | 1090035 | 2009 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Epigenetic Silencing of CRABP2 and MX1 in Head and Neck Tumors
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کلمات کلیدی
TSSTMAqRT-PCRMSPHNSCC5-Aza-2′-deoxycytidine - 5-Aza-2'-deoxycytidinerash - راشtranscription start site - رونویسی شروع سایتTissue microarray - میکروآرشی بافتmethylation-specific polymerase chain reaction - واکنش زنجیره ای پلیمراز متیلاسیون خاصquantitative real-time polymerase chain reaction - واکنش زنجیره ای پلیمراز کمی زمان واقعی استHead and neck squamous cell carcinoma - کارسینوم سلول سنگفرشی سر و گردن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease affecting the epithelium of the oral cavity, pharynx and larynx. Conditions of most patients are diagnosed at late stages of the disease, and no sensitive and specific predictors of aggressive behavior have been identified yet. Therefore, early detection and prognostic biomarkers are highly desirable for a more rational management of the disease. Hypermethylation of CpG islands is one of the most important epigenetic mechanisms that leads to gene silencing in tumors and has been extensively used for the identification of biomarkers. In this study, we combined rapid subtractive hybridization and microarray analysis in a hierarchical manner to select genes that are putatively reactivated by the demethylating agent 5-aza-2â²-deoxycytidine (5Aza-dC) in HNSCC cell lines (FaDu, UM-SCC-14A, UM-SCC-17A, UM-SCC-38A). This combined analysis identified 78 genes, 35 of which were reactivated in at least 2 cell lines and harbored a CpG island at their 5â² region. Reactivation of 3 of these 35 genes (CRABP2, MX1, and SLC15A3) was confirmed by quantitative real-time polymerase chain reaction (PCR; fold change, â¥3). Bisulfite sequencing of their CpG islands revealed that they are indeed differentially methylated in the HNSCC cell lines. Using methylation-specific PCR, we detected a higher frequency of CRABP2 (58.1% for region 1) and MX1 (46.3%) hypermethylation in primary HNSCC when compared with lymphocytes from healthy individuals. Finally, absence of the CRABP2 protein was associated with decreased disease-free survival rates, supporting a potential use of CRABP2 expression as a prognostic biomarker for HNSCC patients.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 11, Issue 12, December 2009, Pages 1329-1339, IN7-IN9
Journal: Neoplasia - Volume 11, Issue 12, December 2009, Pages 1329-1339, IN7-IN9
نویسندگان
Marilia F. Calmon, Rodrigo V. Rodrigues, Carla M. Kaneto, Ricardo P. Moura, Sabrina D. Silva, Louise Danielle C. Mota, Daniel G. Pinheiro, Cesar Torres, Alex F. de Carvalho, PatrÃcia M. Cury, Fabio D. Nunes, Ines Nobuko Nishimoto, Fernando A. Soares,