Journal
BIOCHEMICAL PHARMACOLOGY
Volume 75, Issue 6, Pages 1292-1301Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2007.11.017
Keywords
TGF-beta 1; chondrosarcoma; integrin; migration; NF-kappa B
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Transforming growth factor-beta 1 (TGF-beta 1) plays an essential role in tumor progression and metastasis. Integrins are the major adhesive molecules in mammalian cells. Here we found that TGF-beta 1 increased the migration and cell surface expression of alpha v beta 3 integrin in human chondrosarcoma cells (JJ012 cells). Phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002) or Akt inhibitor inhibited the TGF-beta 1-induced increase the migration of chondrosarcoma cells. TGF-beta 1 stimulation increased the phosphorylation of p85 subunit of PI3K, and serine 473 of Akt. In addition, treatment of JJ102 cells with NF-kappa B inhibitor (PDTC) or I kappa B protease inhibitor (TPCK) inhibited TGF-beta 1-induced cells migration and integrins expression. Treatment of JJ012 cells with TGF-beta 1-induced I kappa B kinase alpha/beta (IKK alpha/beta) phosphorylation, I kappa B alpha phosphorylation, p65 Ser(536) phosphorylation, and kappa B-luciferase activity. The TGF-beta 1-mediated increases in IKK alpha/beta phosphorylation and p65 Ser(536) phosphorylation were inhibited by Ly294002 and Akt inhibitor. Cotransfection with p85 and Akt mutants also reduced the TGF-beta 1-induced kappa B-luciferase activity. Taken together, these results suggest that the TGF-beta 1 acts through PI3K/Akt, which in turn activates IKK alpha/beta and NF-kappa B, resulting in the activations of alpha v beta 3 integrins and contributing the migration of chondrosarcoma cells. (c) 2007 Elsevier Inc. All rights reserved.
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