کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3299621 | 1209933 | 2006 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Correlation Between the Single-Site CpG Methylation and Expression Silencing of the XAF1 Gene in Human Gastric and Colon Cancers
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کلمات کلیدی
TSAGAPDHBSPIAPMSPXIAP5′-Aza-2′-deoxycytidineXAF1Trichostatin A - تریکوستاتین Ainhibitor of apoptosis protein - مهار کننده پروتئین آپوپتوزیسNucleotide - نوکلئوتیدpolymerase chain reaction - واکنش زنجیره ای پلیمرازmethylation-specific polymerase chain reaction - واکنش زنجیره ای پلیمراز متیلاسیون خاصPCR - واکنش زنجیرهٔ پلیمرازX-linked Inhibitor of Apoptosis Protein - پروتئین آپوپتوز وابسته به X-linkedglyceraldehyde-3-phosphate dehydrogenase - گلیسرالیدید-3-فسفات دهیدروژناز
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: X-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) antagonizes the anti-caspase activity of XIAP. XAF1 messenger RNA is present in normal tissues but undetectable in various cancers and thus poses a potential tumor suppressor gene. The aim of this study was to examine the novel pattern of methylation of XAF1 in gastric and colon cancers and locate the important CpG sites for transcriptional regulation and tumor progression. Methods: XAF1 expression was detected by reverse-transcription polymerase chain reaction (PCR) and Western blot analysis. Four different fragments around the transcription start site of XAF1 were cloned and examined putative promoter activities by luciferase reporter assay. Each CpG site in fragment F291 was mutated by site-directed mutagenesis technique, and the change of promoter activity of this fragment was detected by luciferase reporter assay. Methylation status of XAF1 was determined by methylation-specific PCR (MSP) and bisulfite DNA sequencing PCR analysis. Results: Down-regulation of XAF1 in association with hypermethylation was detected in 3 of 4 human gastric cancer cell lines and 6 of 8 colon cancer cell lines. Of the 4 promoter fragments, F291 showed the highest promoter activity, which could be down-regulated obviously by the mutation of particular CpG sites. Moreover, aberrant hypermethylation of these important CpG sites was strongly associated with the development of gastric and colon cancers. Conclusions: A cluster of methylated CpG sites instead of CpG islands located in the promoter area resulted in gene silencing of XAF1, and CpGs at â2nd, â1st, and +3rd positions are functionally more important in its transcriptional regulation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 131, Issue 6, December 2006, Pages 1835-1843
Journal: Gastroenterology - Volume 131, Issue 6, December 2006, Pages 1835-1843
نویسندگان
Bing Zou, Chor Sang Chim, Hui Zeng, Suet Yi Leung, Yi Yang, Shui Ping Tu, Marie C.M. Lin, Jide Wang, Hua He, Shi Hu Jiang, Yun Wei Sun, Li Fen Yu, Siu Tsan Yuen, Hsiang Fu Kung, Benjamin C.Y. Wong,