کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2152349 1090066 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
siRNA-Mediated β-Catenin Knockdown in Human Hepatoma Cells Results in Decreased Growth and Survival *
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
siRNA-Mediated β-Catenin Knockdown in Human Hepatoma Cells Results in Decreased Growth and Survival *
چکیده انگلیسی

β-Catenin, the chief oncogenic component of the canonical Wnt pathway, is known to be involved in a variety of cancers, including hepatocellular carcinoma (HCC). Although the mechanism of β-catenin activation in HCC is multifactorial, it is indisputably implicated at various stages of hepatocarcinogenesis, making it an attractive therapeutic target. Here we investigate the effect of small interfering RNA-mediated β-catenin knockdown on the growth and survival of human hepatoma cell lines with (HepG2) and without (Hep3B) β-catenin mutations. Transfection of HepG2 and Hep3B cells with human β-catenin (CTNNBl) small interfering RNA resulted in a significant β-catenin decrease, as confirmed by Western blot analyses and immunofluorescence, also leading to decreased expression of known target genes such as cyclin D1 and glutamine synthetase. The decrease in β-catenin activity was confirmed by TOPflash reporter luciferase assay. The functional impact of diminished β-catenin was exhibited as temporal decrease in tumor cell viability by the MTT assay. A concomitant decrease in tumor cell proliferation was also evident with [3H]thymidine incorporation and verified with soft agar assays. Thus, β-catenin is essential for the survival and growth of hepatoma cells independent of mutations in the β-catenin gene and provide a proof of principle for the significance of the therapeutic inhibition of β-catenin in HCC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neoplasia - Volume 9, Issue 11, November 2007, Pages 951-959