کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10904260 | 1086569 | 2013 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Polyamine and methionine adenosyltransferase 2A crosstalk in human colon and liver cancer
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کلمات کلیدی
scrambled siRNAAP-1EGFIGF-1Ornithine decarboxylaseODC5-bromo-2′-deoxyuridine - 5-bromo-2'-deoxyuridineHCC - HCCSmall interfering RNA - RNA تداخل کوچکsiRNA - siRNAS-adenosylmethionine - اس-ادنوزیل متیونینinsulin-like growth factor-1 - انسولین مانند عامل رشد 1chromatin immunoprecipitation - ایمن سازی کروماتینBrdU - بروموداکسی اوریدینLiver cancer - سرطان کبدColon cancer - سرطان کولونepidermal growth factor - عامل رشد اپیدرمیputrescine - قرار دادنMat - ماتmethionine adenosyltransferase - متیونین آدنوزیلت ترانسفرازpolymerase chain reaction - واکنش زنجیره ای پلیمرازPCR - واکنش زنجیرهٔ پلیمرازactivator protein-1 - پروتئین فعال کننده-1CHiP - چیپHepatocellular carcinoma - کارسینوم هپاتوسلولار(کارسینوم سلولهای استخوانی)high-performance liquid chromatography - کروماتوگرافی مایعی کاراHPLC - کروماتوگرافی مایعی کاراSAMe - یکسان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Methionine adenosyltransferase (MAT) is an essential enzyme that is responsible for the biosynthesis of S-adenosylmethionine (SAMe), the principal methyl donor and precursor of polyamines. MAT1A is expressed in normal liver and MAT2A is expressed in all extrahepatic tissues. MAT2A expression is increased in human colon cancer and in colon cancer cells treated with mitogens, whereas silencing MAT2A resulted in apoptosis. The aim of the current work was to examine the mechanism responsible for MAT2A-dependent growth and apoptosis. We found that in RKO (human adenocarcinoma cell line) cells, MAT2A siRNA treatment lowered cellular SAMe and putrescine levels by 70-75%, increased apoptosis and inhibited growth. Putrescine supplementation blunted significantly MAT2A siRNA-induced apoptosis and growth suppression. Putrescine treatment (100Â pmol/L) raised MAT2A mRNA level to 4.3-fold of control, increased the expression of c-Jun and c-Fos and binding to an AP-1 site in the human MAT2A promoter and the promoter activity. In human colon cancer specimens, the expression levels of MAT2A, ornithine decarboxylase (ODC), c-Jun and c-Fos are all elevated as compared to adjacent non-tumorous tissues. Overexpression of ODC in RKO cells also raised MAT2A mRNA level and MAT2A promoter activity. ODC and MAT2A are also overexpressed in liver cancer and consistently, similar MAT2A-ODC-putrescine interactions and effects on growth and apoptosis were observed in HepG2 cells. In conclusion, there is a crosstalk between polyamines and MAT2A. Increased MAT2A expression provides more SAMe for polyamines biosynthesis; increased polyamine (putrescine in this case) can activate MAT2A at the transcriptional level. This along with increased ODC expression in cancer all feed forward to further enhance the proliferative capacity of the cancer cell.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 319, Issue 12, 15 July 2013, Pages 1902-1911
Journal: Experimental Cell Research - Volume 319, Issue 12, 15 July 2013, Pages 1902-1911
نویسندگان
Maria Lauda Tomasi, Minjung Ryoo, Anna Skay, Ivan Tomasi, Pasquale Giordano, José M. Mato, Shelly C. Lu,