RESTORATION OF CELL-TO-CELL COMMUNICATION IN THYROID-CELL LINES BY TRANSFECTION WITH AND STABLE EXPRESSION OF THE CONNEXIN-32 GENE - IMPACTON CELL-PROLIFERATION AND TISSUE-SPECIFIC GENE-EXPRESSION

Normal thyroid epithelial cells coexpress connexin-32 and connexin-43, which form distinct gap functions. In primary culture, connexin-43 is expressed by thyrocytes in monolayers or reorganized into follicles, whereas the, expression of eonnexin-32 is dependent upon the reconstit ution of follicles, To study the functional impact of connexin-32 gap junctions in thyroid cells, we transfected connexin-32 cDNA in two thy roid-derived communication-deficient cell lines, FRT and FRTL-5. The s elected clones, which stably expressed connexin-32 at high levels and exhibited high gap junction-mediated dye-coupling, presented a reduced proliferation rate as compared with that of the corresponding wild-ty pe FRT and FRTL-5 cells; the mean population doubling time was increas ed by similar to 35%, The proliferation of connexin-32-transfected FRT L-5 cells remained thyrotropin-dependent; the range of thyrotropin con centrations that stimulated growth was the same in transfected and con trol cells, The expression of connexin-32 led to an increase of thyrog lobulin gene expression in FRTL-5 cells, The expression of two other t issue-specific proteins, thyroid transcription factor-1 and Pax-8, was unchanged, These findings provide evidence that connexin-32 gap junct ion-mediated cell-to-cell communication participates in the control of growth and differentiation of thyroid cells.