RRC ID 61899
Author Wei YY, Chen YJ, Hsiao YC, Huang YC, Lai TH, Tang CH.
Title Osteoblasts-derived TGF-beta1 enhance motility and integrin upregulation through Akt, ERK, and NF-kappaB-dependent pathway in human breast cancer cells.
Journal Mol Carcinog
Abstract Bone metastases are common complications of breast cancer. Integrins are the major adhesive molecules in mammalian cells. Here we found that osteoblast conditioned medium (OBCM) increased the migration and cell surface expression of beta1 or beta3 integrin in human breast cancer cells (MDA-MB-231 cells). beta1 or beta3 integrin monoclonal antibodies (mAbs) or small interference RNA (siRNA) against beta1 or beta3 integrin inhibited the OBCM-induced increase in the migration of breast cancer cells. Transforming growth factor-beta1 (TGF-beta1) siRNA could remarkably blocked OBCM-induced chemomigration and beta1 and beta3 integrin expression in breast cancer cells. Stimulation of cells with OBCM caused an increase in Akt and extracellular signal-regulated kinase (ERK) phosphorylation in a time-dependent manner. In addition, treatment of MDA-MB-231 cells with phosphatidylinositol 3-kinase inhibitor (LY294002), ERK inhibitor (PD98059), NF-kappaB inhibitor (PDTC), or IkappaB protease inhibitor (TPCK) inhibited OBCM-induced cells migration and integrins expression. Treatment of MDA-MB-231 cells with OBCM induced IkappaB kinase alpha/beta (IKK alpha/beta) phosphorylation, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity. The OBCM-mediated increases in IKK alpha/beta phosphorylation, p65 Ser(536) phosphorylation, and kappaB-luciferase activity were inhibited by LY294002 and PD98059. In addition, TGF-beta1 siRNA also reduced the OBCM-induced ERK, Akt, IKKalpha/beta, IkappaBalpha, and p65 phosphorylation. Taken together, these results suggest that the osteoblast-derived TGF-beta1 acts through Akt and ERK, which in turn activates IKKalpha/beta and NF-kappaB, resulting in the activations of beta1 and beta3 integrins and contributing the migration of breast cancer cell.
Volume 47(7)
Pages 526-37
Published 2008-7-1
DOI 10.1002/mc.20411
PMID 18161870
MeSH Animals Blotting, Western Breast Neoplasms / metabolism* Breast Neoplasms / pathology Cell Movement Culture Media, Conditioned / pharmacology Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases / metabolism* Flow Cytometry Humans I-kappa B Kinase / genetics I-kappa B Kinase / metabolism I-kappa B Proteins / genetics I-kappa B Proteins / metabolism Integrin beta1 / metabolism* Integrin beta3 / metabolism* Luciferases / metabolism Mice NF-KappaB Inhibitor alpha NF-kappa B / antagonists & inhibitors NF-kappa B / genetics NF-kappa B / metabolism* Osteoblasts / metabolism* Phosphorylation Proto-Oncogene Proteins c-akt / metabolism* Signal Transduction Transfection Transforming Growth Factor beta1 / metabolism* Tumor Cells, Cultured Up-Regulation
IF 3.825
Human and Animal Cells MC3T3-E1(RCB1126)