Transient activation of c-Jun NH2-terminal kinase by growth factors influences survival but not apoptosis of human thyrocytes

Activation of e-Jun NH2-terminal kinase (JNK), a member of the mitogen-acti vated protein kinase (MAPK) family, is involved in apoptosis or cell prolif eration We have previously demonstrated that ionizing radiation or thyroid- stimulating hormone activated JNK without linking to thyroid cell apoptosis . To clarify the involvement of JNK activation in thyroid cell survival, we investigated the effects of various growth factors on induction of JNK act ivation in cultured human thyroid cells. JNK activation was observed at 30 minutes after fetal bovine serum (FBS) stimulation and returned to basal le vel at 240 minutes. Epidermal growth factor (EGF), transforming,growth fact or-beta (TGF-beta) and hepatocyte growth factor (HGF) also induced JNK acti vation, but did not trigger apoptotic cell death. Furthermore, we observed high basal activation of JNK in four of five human thyroid cancer cell line s. Overexpression of c-Met, an HGF receptor, was observed in two of the fou r cell lines with high basal JNK activity. Our results suggest that JNK act ivation does not induce apoptosis but is associated with survival or transf ormation of human thyroid cells.