title: Thyroglobulin (Tg) activates MAPK pathway to induce thyroid cell growth in the absence of TSH, insulin and serum.
abstract: The growth of thyroid cells is tightly regulated by thyroid stimulating hormone (TSH) through the cyclic adenosine 3', 5'-monophosphate (cAMP) signaling pathway by potentiating the mitogenic activity of insulin and insulin-like growth factors (IGFs). However, we recently reported that thyroglobulin (Tg), a major product of the thyroid, also induces the growth of thyroid cells cultured in 0.2% serum in the absence of TSH and insulin. In this report, we demonstrate that Tg induced phosphorylation of molecules of the c-Raf/MEK/ERK pathway of the mitogen-activated protein kinase (MAPK). The MEK-1/2 inhibitor PD98059 suppressed Tg-induced phosphorylation of ERK1/2 and reduced bromodeoxyuridine (BrdU) incorporation. Tg also induced expression of the essential transcriptional factors c-Myc, c-Fos and c-Jun and phosphorylation of the retinoblastoma (Rb) protein. The present results, together with the previous report, suggest that Tg utilizes multiple signaling cascades to induce thyroid cell growth independent of TSH/cAMP stimulation.
authors.affiliation: Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo 189-0002, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sue
authors.forename: Moyuru
authors.initials: M
authors.lastname: Hayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Akama
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanigawa
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshihara
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishido
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Norihisa
authors.initials: N
authors.lastname: Ishii
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000096:biosynthesis*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis*; D051381:Rats; D013954:Thyroglobulin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013972:Thyrotropin / Q000494:pharmacology
chemical_list: D016895:Culture Media, Serum-Free; D005419:Flavonoids; D007328:Insulin; D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D013972:Thyrotropin; D013954:Thyroglobulin; D019908:Proto-Oncogene Proteins c-raf; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one