MUTATED HUMAN KIRSTEN RAS, DRIVEN BY A THYROGLOBULIN PROMOTER, INDUCES A GROWTH ADVANTAGE AND PARTIALLY DEDIFFERENTIATES RAT-THYROID EPITHELIAL-CELLS IN-VITRO

We have earlier shown that expression of the human activated Ki-ras, d irected by the rat thyroglobulin CTG) promoter in the thyroid gland of transgenic mice, is able to induce thyroid benign tumors, albeit at l ow incidence. A likely explanation of our results is that the low leve ls of exogenous Ki-ras transcripts are not sufficient to induce multif ocal tumors in the thyroid gland. We have performed experiments to ana lyze the effects of a similar construct in vitro upon thyroid-cell pro liferation and differentiation. Transfection of FRTL-5 rat thyroid cel ls with the human Ki-ras(val12) fused to the rat TG promoter is rapidl y followed by reduced expression of the differentiation markers thyrog lobulin, thyroperoxydase and thyrotropin receptor, but not by fully ma lignant cell transformation. The data reported support the hypothesis that Ki-ras mRNA levels are critical to the process of complete neopla stic transformation of thyroid epithelial differentiated cells in vitr o. (C) 1995 Wiley-Liss, Inc.