کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4304155 1288497 2007 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Rat Adenocarcinoma Cell Line Infected With an Adenovirus Carrying a Novel Herpes-Simplex Virus-Thymidine Kinase Suicide Gene Construct Dies by Apoptosis Upon Treatment with Ganciclovir
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Rat Adenocarcinoma Cell Line Infected With an Adenovirus Carrying a Novel Herpes-Simplex Virus-Thymidine Kinase Suicide Gene Construct Dies by Apoptosis Upon Treatment with Ganciclovir
چکیده انگلیسی

BackgroundEukaryotic initiation factor 4E (eIF4E) facilitates the translation of mRNAs with long 5′ untranslated regions and thus regulates protein synthesis. This protein has been found in elevated quantities in breast, colon, and head and neck cancers. To exploit this dysfunction, the 619 base pair 5′ untranslated regions of fibroblast growth factor-2 was spliced upstream of the herpes simplex virus thymidine kinase gene in an adenovirus vector (Ad-HSV-UTK), with the expectation that TK will be expressed in cells that overexpress eIF4E and, thus, render these cells susceptible to ganciclovir. In this study, we investigated the in vitro activity of this suicide gene therapy against the rat Mat BIII breast adenocarcinoma cell line, and assessed whether apoptosis was the responsible mechanism of cell killing.MethodsMat BIII cells were infected with Ad-HSV-UTK, and optimal multiplicity of infection was determined using green fluorescent protein tagged adenovirus. Western blot analysis was used to detect eIF4E and TK expression. Cell viability was assessed by the MTT assay. Induction of apoptosis was determined using annexin V-FITC and propidium iodine detection kit and a terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling in situ cell death detection kit.ResultsWestern Blot analysis confirmed successful infection of the cell line. Marked cytotoxicity was noted by the MTT assay in the infected group with a 100-fold less concentration of ganciclovir compared with the control groups. Annexin V-FITC/propidium iodide revealed apoptosis in infected cells following treatment with ganciclovir.ConclusionSuicide gene therapy targeting the overexpression of eIF4E induces apoptosis and cell death in rat Mat BIII mammary adenocarcinoma cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 143, Issue 1, November 2007, Pages 189–194
نویسندگان
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