Thyroglobulin (Tg) activates MAPK pathway to induce thyroid cell growth in the absence of TSH, insulin and serum

Mariko Sue; Moyuru Hayashi; Akira Kawashima; Takeshi Akama; Kazunari Tanigawa; Aya Yoshihara; Takeshi Hara; Yuko Ishido; Tetsuhide Ito; Shin-Ichiro Takahashi; Norihisa Ishii; Koichi Suzuki

doi:10.1016/j.bbrc.2012.03.046

Thyroglobulin (Tg) activates MAPK pathway to induce thyroid cell growth in the absence of TSH, insulin and serum

Biochem Biophys Res Commun. 2012 Apr 13;420(3):611-5. doi: 10.1016/j.bbrc.2012.03.046. Epub 2012 Mar 16.

Authors

Mariko Sue¹, Moyuru Hayashi, Akira Kawashima, Takeshi Akama, Kazunari Tanigawa, Aya Yoshihara, Takeshi Hara, Yuko Ishido, Tetsuhide Ito, Shin-Ichiro Takahashi, Norihisa Ishii, Koichi Suzuki

Affiliation

¹ Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo 189-0002, Japan.

PMID: 22445893
DOI: 10.1016/j.bbrc.2012.03.046

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Cell Proliferation / drug effects*
Culture Media, Serum-Free / pharmacology
DNA Replication / drug effects
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / biosynthesis*
Flavonoids / pharmacology
Gene Expression / drug effects
Insulin / pharmacology
MAP Kinase Kinase Kinases / biosynthesis*
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-fos / metabolism
Proto-Oncogene Proteins c-jun / metabolism
Proto-Oncogene Proteins c-myc / metabolism
Proto-Oncogene Proteins c-raf / biosynthesis*
Rats
Thyroglobulin / pharmacology*
Thyroid Gland / cytology
Thyroid Gland / drug effects*
Thyroid Gland / enzymology
Thyrotropin / pharmacology

Substances

Culture Media, Serum-Free
Flavonoids
Insulin
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-fos
Proto-Oncogene Proteins c-jun
Proto-Oncogene Proteins c-myc
Thyrotropin
Thyroglobulin
Proto-Oncogene Proteins c-raf
Extracellular Signal-Regulated MAP Kinases
MAP Kinase Kinase Kinases
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one