Inhibition of c-ras reactivates thyroglobulin synthesis in middle-T transformed thyroid cells.
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.
Di Jeso
B
B
Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche, Universita Federico II, Medical School, Naples, Italy.
Feliciello
A
A
Pacifico
F
F
Iannelli
A
A
D'Armiento
F
F
Liguoro
D
D
Giuliano
P
P
Ferulano
G
G
Avvedimento
E V
EV
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D000242:Cyclic AMP / Q000096:biosynthesis; D011905:Genes, ras; D007455:Iodine / Q000378:metabolism; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011989:Receptors, Thyrotropin / Q000235:genetics; D015398:Signal Transduction; D013954:Thyroglobulin / Q000096:biosynthesis*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology / Q000502:physiology; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D000952:Antigens, Polyomavirus Transforming; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D013954:Thyroglobulin; D007455:Iodine; D000242:Cyclic AMP; D018631:ras Proteins