کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2130700 1086596 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Mixed lineage kinase 3 is required for matrix metalloproteinase expression and invasion in ovarian cancer cells
چکیده انگلیسی

Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAP3K) that activates MAPK signaling pathways and regulates cellular responses such as proliferation, migration and apoptosis. Here we report high levels of total and phospho-MLK3 in ovarian cancer cell lines in comparison to immortalized nontumorigenic ovarian epithelial cell lines. Using small interfering RNA (siRNA)-mediated gene silencing, we determined that MLK3 is required for the invasion of SKOV3 and HEY1B ovarian cancer cells. Furthermore, mlk3 silencing substantially reduced matrix metalloproteinase (MMP)-1, -2, -9 and -12 gene expression and MMP-2 and -9 activities in SKOV3 and HEY1B ovarian cancer cells. MMP-1, -2, -9 and-12 expression, and MLK3-induced activation of MMP-2 and MMP-9 requires both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activities. In addition, inhibition of activator protein-1 (AP-1) reduced MMP-1, MMP-9 and MMP-12 gene expression. Collectively, these findings establish MLK3 as an important regulator of MMP expression and invasion in ovarian cancer cells.


► Ovarian cancer cell lines have high levels of total and phosphorylated MLK3.
► MLK3 is required for MMP expression and activity in ovarian cancer cells.
► MLK3 is required for invasion of SKOV3 and HEY1B ovarian cancer cells.
► MLK3-dependent regulation of MMP-2 and MMP-9 activities requires ERK and JNK.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 318, Issue 14, 15 August 2012, Pages 1641–1648
نویسندگان
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