Transforming growth factor-β and epidermal growth factor synergistically stimulate epithelial to mesenchymal transition (EMT) through a MEK-dependent mechanism in primary cultured pig thyrocytes

• DOI: 10.1242/jcs.00091
• Publication Date: 2002-11-14T20:00:39Z
• Authors: Mats Grände; Åsa Franzen; Jan-Olof Karlsson; Lars E. Ericson; Nils-Erik Heldin; Mikael Nilsson
• Keywords: Adherens junction

Enhancement of tumor cell growth and invasiveness by transforming factor-β (TGF-β) requires constitutive activation the ras/MAPK pathway. Here we have investigated how MEK epidermal factor (EGF) influences response fully differentiated growth-arrested pig thyroid epithelial cells in primary culture to TGF-β1. The tightness was maintained after single stimulation with EGF or TGF-β1 (both 10 ng/ml) for 48 hours. In contrast, co-stimulation abolished transepithelial resistance increased paracellular flux [3H]inulin within 24 Reduced levels tight junction proteins claudin-1 occludin accompanied loss barrier function. N-cadherin, expressed only few untreated single-stimulated cultures, at same time 30-fold co-localised E-cadherin adherens junctions all cells. After hours co-stimulation, both E- N-cadherin were downregulated attained a fibroblast-like morphology formed multilayers. partially inhibited EGF-induced Erk phosphorylation. inhibitor U0126 prevented residual phosphorylation abrogated synergistic responses EGF. observations indicate that concomitant factor-induced is necessary convert normal mesenchymal phenotype.