Studies on the role of c-fos in TSH-stimulated thyroid cell proliferation.

TSH stimulates proliferation of FRTL5 rat thyroid cells, and also increases c-fos mRNA levels in these cells. We therefore investigated the role of c-fos in TSH-mediated FRTL5 cell proliferation. FRTL5 cells were stably transfected with plasmid constructs that transcribe, under the control of the dexamethasone-inducible MMTV promoter, a 5'-fragment (84 nucleotides) of c-fos mRNA, either in the sense or in the antisense orientation. Four c-fos antisense clones (A1, A2, A3, A4), one sense clone (S2), and wild-type (untransfected) FRTL5 cells were studied. Southern blot analysis indicated similar levels of transgenome in all transfected cell lines. Antisense clone A3 exhibited the greatest dexamethasone-induced growth inhibition, two times (59% vs. 30%) greater than that in control, sense c-fos-transfected or wild-type FRTL5, cells. Consistent with the degree of growth inhibition, northern blot analysis revealed that c-fos antisense clone A3 expressed the highest levels of c-fos antisense transcript. However, we did not observe dexamethasone induction of the antisense c-fos-beta globin hybrid mRNA in any clone, including clone A3. Taken together, our results provide circumstantial evidence that c-fos, at least in part, may play a role in TSH-mediated thyroid cell growth.