Transient activation of c-Jun NH2-terminal kinase by growth factors influences survival but not apoptosis of human thyrocytes.
Activation of c-Jun NH2-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is involved in apoptosis or cell proliferation. 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 activation in cultured human thyroid cells. JNK activation was observed at 30 minutes after fetal bovine serum (FBS) stimulation and returned to basal level at 240 minutes. Epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) also induced JNK activation, but did not trigger apoptotic cell death. Furthermore, we observed high basal activation of JNK in four of five human thyroid cancer cell lines. Overexpression of c-Met, an HGF receptor, was observed in two of the four cell lines with high basal JNK activity. Our results suggest that JNK activation does not induce apoptosis but is associated with survival or transformation of human thyroid cells.
Shklyaev
S S
SS
Department of Nature Medicine, Atomic Bomb Disease Institute, Nagasaki University School of Medicine, Japan.
Namba
H
H
Mitsutake
N
N
Alipov
G
G
Nagayama
Y
Y
Maeda
S
S
Ohtsuru
A
A
Tsubouchi
H
H
Yamashita
S
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002417:Cattle / Q000097:blood / Q000196:embryology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation; D005312:Fetal Blood; D006133:Growth Substances / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000473:pathology; D013997:Time Factors
D006133:Growth Substances; D017228:Hepatocyte Growth Factor; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases