TGF-beta1 actions on FRTL-5 cells provide a model for the physiological regulation of thyroid growth.
Little is known about the TGF-beta1 mechanism that promotes thyroid cell growth arrest. We assessed TGF-beta1 effects on Fisher rat thyroid cell line (FRTL-5). This allowed us to study TGF-beta1 action on thyroid cells in various physiological situations such as actively proliferating cells, resting cells stimulated to proliferate by the action of various mitogens, and resting cells. TGF-beta1 arrested proliferating FRTL-5 cells, increasing c-myc mRNA levels and reducing p27-free cyclin D1 protein levels, without affecting either the cellular content of p27 or the cyclin D1-p27 complexes. Moreover, TGF-beta1 treatment reduced the activity of cyclin E-CDK2 complexes and, consequently, pRB was found to be hypophosphorylated. TGF-beta1 prevented resting cells to enter in the cell cycle when stimulated with growing medium (newborn calf serum plus a mixture of five hormones) but not when TSH (thyroid stimulating hormone) plus IGF-1 (Insulin-like growth factor I) were used as mitogens. Both stimuli increased the levels of cyclins D1, D3 and E but TGF-beta1 had a greater effect in decreasing these cyclin levels in growing-medium stimulated cells than in TSH + IGF-1. This suggests that for FRTL-5 cells, the content of these cyclins must exceed a threshold to progress through the cell cycle. TGF-beta1 induced apoptosis in quiescent cells, accompanied by a reduction in p27 protein levels and an increase in c-myc expression. Interestingly, TGF-beta1-induced variations in prothymosin alpha and c-myc mRNA levels were not correlated. TGF-beta1 always promoted an increase of p15 mRNA levels. In summary, our results point to the fact that TGF-beta1 could play a physiological role in the control of thyroid growth through the modification of cell cycle regulatory proteins.
Carneiro
C
C
Departamento de Fisiología, Laboratorio de Neurociencia Ramón Domínguez, Santiago de Compostela, Spain.
Alvarez
C V
CV
Zalvide
J
J
Vidal
A
A
Domínguez
F
F
D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D008954:Models, Biological; D051381:Rats; D011916:Rats, Inbred F344; D013961:Thyroid Gland / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D016212:Transforming Growth Factor beta