کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3318392 1211599 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effect of c-MYC and E2F1 Gene Silencing and of 5-Azacytidine Treatment on Telomerase Activity in Pancreatic Cancer-Derived Cell Lines
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Effect of c-MYC and E2F1 Gene Silencing and of 5-Azacytidine Treatment on Telomerase Activity in Pancreatic Cancer-Derived Cell Lines
چکیده انگلیسی
Background:The gene promoter region of human telomerase reverse transcriptase (hTERT) contains binding sites for c-myc and E2F1 as well as CpG islands, suggesting regulation by genetic factors and epigenetically by methylation. Hence, the effect of the demethylating agent 5-azacytidine and silencing of c-MYC and E2F1 genes on its expression and consequently on telomerase activity were studied in pancreatic cancer-derived cell lines. Methods: MlaPaCa-2 and PANC-1 cell lines were transfected with SiRNA against E2F1 and c-MYC genes separately as well as along with 5-azacytidine treatment. The hTERT gene methylation status was determined by methylation-specific PCR and telomerase activity quantitated by TRAP-PCR-ELISA. Results: Demethylation by 5-azacytidine resulted in hTERTinhibition with a reduction in telomerase activity to 37-49% of controls. Silencing of E2F-1 or c-MYC also decreased the hTERT transcript and telomerase activity with a more pronounced effect with respect to c-MYC silencing. There was a synergistic effect of demethylation and gene silencing on the inhibition of hTERT mRNA expression which resulted in undetectable levels of telomerase activity. Conclusion: Telomerase activity, which is necessary for cellular immortalization, can be shut down by a combined approach using SiRNA-mediated gene silencing and demethylating agents, which has therapeutic implications.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pancreatology - Volume 9, Issue 4, June 2009, Pages 360-368
نویسندگان
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