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

Abstract

We have analysed the expression of cadherin/catenin complex molecules in PC CI3 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, adeno-virus E1A, ras, raf, myc + ras, E1A + raf. However, ras- and raf-transformed PC CI3 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 β1 integrin localization was observed in areas where this altered pattern of E-cadherin expression was detected. However, β1 integrin subunit expression was detected at areas of cell-cell contact where E-cadherin showed a normal pattern of expression. Furthermore, ras- and raf-transformed PC CI3 cells showed the ability to migrate in collagen gels, in contrast to their normal untransformed counterpart. Overexpression of β1 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.