کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3296223 | 1209866 | 2008 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
DNA Hypermethylation Contributes to Incomplete Synthesis of Carbohydrate Determinants in Gastrointestinal Cancer
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کلمات کلیدی
N-acetylgalactosaminyltransferasemAbFUTN-acetylgalactosamineGalNAc5-Aza-dCGAPDHCOBRADnmt5-Aza-2′-deoxycytidine - 5-Aza-2'-deoxycytidineDNA methyltransferase - DNA متیل ترانسفرازMonoclonal antibody - آنتی بادی مونوکلونالEBV - اپشتین بار ویروسcombined bisulfite restriction analysis - تجزیه و تحلیل محدود بیسولفیتGastrointestinal - دستگاه گوارشSialyltransferase - سیالیال ترانسفرازfucosyltransferase - فوکوسیل ترانسفرازHelicobacter pylori - هلیکوباکتر پیلوریEpstein-Barr virus - ویروس Epstein-BarrGal - گالGalactose - گالاکتوزمی glyceraldehyde-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: It has long been known that malignant transformation is associated with abnormal expression of carbohydrate determinants. The aim of this study was to clarify the cause of cancer-associated abnormal glycosylation in gastrointestinal (GI) cancers. Methods: We compared the expression levels of “glyco-genes,” including glycosyltransferases and glycosidases, in normal GI mucosa and in gastric and colorectal cancer cells. To examine the possibility that DNA hypermethylation contributed to the down-regulation of these genes, we treated GI cancer cells with 5-aza-2â²-deoxycytidine (5-aza-dC), an inhibitor of DNA methyltransferase. Results: The silencing of some of these glyco-genes, but not up-regulation of certain molecules, was observed. The Sda carbohydrate was abundantly expressed in the normal GI mucosa, but its expression was significantly decreased in cancer tissues. When human colon and gastric cancer cells were treated with 5-aza-dC, cell surface expression of Sda and the transcription of B4GALNT2, which catalyzes the synthesis of the Sda, were induced. The promoter region of the human B4GALNT2 gene was heavily hypermethylated in many of the GI cancer cell lines examined as well as in gastric cancer tissues (39 out of 78 cases). In addition, aberrant methylation of the B4GALNT2 gene was strongly correlated with Epstein-Barr virus-associated gastric carcinomas and occurred coincidentally with hypermethylation of the ST3GAL6 gene. Conclusions: Epigenetic changes in a group of glycosyltransferases including B4GALNT2 and ST3GAL6 represent a malignant phenotype of gastric cancer caused by silencing of the activity of these enzymes, which action may eventually induce aberrant glycosylation and expression of cancer-associated carbohydrate antigens.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 135, Issue 1, July 2008, Pages 142-151.e3
Journal: Gastroenterology - Volume 135, Issue 1, July 2008, Pages 142-151.e3
نویسندگان
Yuki I. Kawamura, Minoru Toyota, Rei Kawashima, Teruki Hagiwara, Hiromu Suzuki, Kohzoh Imai, Yasuhisa Shinomura, Takashi Tokino, Reiji Kannagi, Taeko Dohi,