کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2775132 1152312 2014 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Decreased expression and prognostic role of cytoplasmic BRSK1 in human breast carcinoma: Correlation with Jab1 stability and PI3K/Akt pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی بالینی
پیش نمایش صفحه اول مقاله
Decreased expression and prognostic role of cytoplasmic BRSK1 in human breast carcinoma: Correlation with Jab1 stability and PI3K/Akt pathway
چکیده انگلیسی

ObjectiveJun activation domain-binding protein 1 (Jab1) was overexpressed in breast cancer, which was involved in degradation of the cyclin-dependent kinase inhibitor p27Kip1. The objective of this study was to examine the effect of brain specific kinase 1 (BRSK1) expression on Jab1 over-expression and related signaling pathway in breast cancer.MethodsImmunohistochemical analysis was performed in 95 human breast carcinoma samples and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for BRSK1 and Jab1 in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction.ResultsWe found that the cytoplasmic BRSK1 expression was inversely associated with Jab1 expression (P < 0.01) and correlated significantly with histologic grade (P = 0.006), however nuclear BRSK1 expression couldn't obtain similar results. Kaplan–Meier analysis revealed that survival curves of low versus high expressers of cytoplasmic BRSK1 and Jab1 showed a highly significant separation in breast cancer (P < 0.01). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of Jab1, phosphor-Akt (p-Akt) was up-regulated, whereas BRSK1 and p27Kip1 were decreased. Treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 could diminish Jab1 expression but increase BRSK1 expression. In addition, we employed siRNA technique to knock down Jab1 and/or BRSK1 expression and observed their effects on MDA-MB-231 cell growth.ConclusionsBRSK1 is a novel tumor suppressor in breast cancer which inversely correlated with Jab1 expression, may involve in the restoring Jab1-induced suppression of p27Kip1 and may regulate cell cycle through the PI3K/Akt pathway.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental and Molecular Pathology - Volume 97, Issue 2, October 2014, Pages 191–201
نویسندگان
, , , , , , , ,