Cell Growth & Differentiation, Vol 6, Issue 10 1315-1319, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Inhibition of c-ras reactivates thyroglobulin synthesis in middle-T transformed thyroid cells

B Di Jeso, A Feliciello, F Pacifico, A Iannelli, F D'Armiento, D Liguoro, P Giuliano, G Ferulano and EV Avvedimento
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Universita Federico II, Medical School, Naples, Italy.

Differentiated thyroid cells expressing polyoma Middle-T became transformed and tumorigenic when injected into syngenic animals. The expression of thyroglobulin was greatly reduced and no longer responsive to thyrotropin (TSH) and to cAMP. Inhibition of endogenous c-ras by the expression of two transdominant negative mutant H-ras genes, Asn17 and Leu61-Ser186, reactivated thyroglobulin synthesis. Reactivation of thyroglobulin synthesis by c-ras inhibition was not observed in the absence of TSH. These findings indicate that MT elicits dedifferentiation of thyroid cells by activating endogenous c-ras and that c-ras interferes with TSH or cAMP signaling.

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