Analysis of codherin/catenin complexes in transformed thyroid epithelial cells: Modulation by beta 1 integrin subunit

We have analysed the expression of cadherin/catenin complex molecules in PC C13 rat thyroid cells transformed in vitro with different oncogenes, No significant downregulation of either E-cadherin, alpha-, beta- and gamma-catenin was detected following the introduction of activated forms of myc, adenovirus E1A, ras, raf, myc + ras, EIA + raf, However, ras- and raf-transformed PC C13 cells showed altered adherens junctions. An altered distribution of cadherin/catenin complexes characterized by radially oriented membrane spikes perpendicular to cell edges was the most prominent feature evidenced by immunofluorescence. No beta 1 integrin localization was observed in areas where this altered pattern of E-cadherin expression was detected. However, beta 1 integrin submit expression was detected at areas of cell-cell contact where E-cadherin showed a normal pattern of expression. Furthermore, ras- and raf-transformed PC C13 cells showed the ability to migrate in collagen gels, in contrast to their normal untransformed counterpart, Overexpression of beta 1 integrin was found to restore normal E-cadherin localization at cell-cell contacts and to partially inhibit the ability to migrate in collagen gels. Finally, two cell lines obtained by ras transformation in vivo, and derived from a rat primary thyroid carcinoma (TK6) and its lung metastasis (MPTK6), were found to have lost gamma-catenin expression. TK6 lost also E-cadherin expression and membrane localization of alpha-catenin, These results suggest that: i) in vitro thyroid cell transformation is associated to a change in cadherin/catenin complexes distribution rather than to a decrease in expression; ii) in vivo transformation is associated to the loss of expression of some of these molecules likely due to tumor progression; iii) alterations in beta 1 integrin subunit expression can result in changes in cadherin/catenin function thus implying that an integrin-cadherin synergy may exist in thyroid cells.