کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2115063 1084570 2008 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Ezrin silencing by small hairpin RNA reverses metastatic behaviors of human breast cancer cells
چکیده انگلیسی

Ezrin primarily acts as a linker between the plasma membrane and the cytoskeleton and is a key component in tumor metastasis. In the present study, RNA interference (RNAi) using ezrin small hairpin RNAs (ezrin shRNAs) was used to define the roles of ezrin in the regulation of malignant behaviors of human breast cancer. The highly metastatic human breast cancer cell MDA-MB-231, in which ezrin mRNA and protein levels are the highest, was selected as a cell model in vitro. In addition, we also found that ezrin expression was up-regulated and its immuno-staining trans-located from cell membrane to cytoplasm, whereas E-cadherin expression decreased and showed the same cell distribution as ezrin in lymphatic metastases of human breast carcinomas. After repression of ezrin by more than 85% of G3PDH and 75% of β-actin in mRNA and protein levels was maintained in the stable expressing ezrin shRNAs MDA-MB-231 cell clones, the abilities of cell motility and invasiveness were obviously inhibited with a 4-fold and 2-fold, respectively, and the altered cell polarity was observed. Western blot analyses further revealed that the silencing of ezrin induced an increased E-cadherin expression and a decreased phosphorylation of β-catenin by inhibiting phosphorylation levels of c-src. These data indicate that ezrin overexpression positively correlated with metastatic potentials of human breast cancer cells, especially lymphatic system metastasis. Decreased ezrin expression by shRNA reversed metastatic behaviors of human breast cancer cells by inducing c-src-mediated E-cadherin expression, suggesting that ezrin may have potential values in assessing lymphatic metastasis of human breast cancers.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 261, Issue 1, 8 March 2008, Pages 55–63
نویسندگان
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