PMID- 22445893 OWN - NLM STAT- MEDLINE DCOM- 20120601 LR - 20180815 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 420 IP - 3 DP - 2012 Apr 13 TI - Thyroglobulin (Tg) activates MAPK pathway to induce thyroid cell growth in the absence of TSH, insulin and serum. PG - 611-5 LID - 10.1016/j.bbrc.2012.03.046 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Sue, Mariko AU - Sue M AD - Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Higashimurayama, Tokyo 189-0002, Japan. FAU - Hayashi, Moyuru AU - Hayashi M FAU - Kawashima, Akira AU - Kawashima A FAU - Akama, Takeshi AU - Akama T FAU - Tanigawa, Kazunari AU - Tanigawa K FAU - Yoshihara, Aya AU - Yoshihara A FAU - Hara, Takeshi AU - Hara T FAU - Ishido, Yuko AU - Ishido Y FAU - Ito, Tetsuhide AU - Ito T FAU - Takahashi, Shin-Ichiro AU - Takahashi S FAU - Ishii, Norihisa AU - Ishii N FAU - Suzuki, Koichi AU - Suzuki K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120316 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Culture Media, Serum-Free) RN - 0 (Flavonoids) RN - 0 (Insulin) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Proto-Oncogene Proteins c-myc) RN - 9002-71-5 (Thyrotropin) RN - 9010-34-8 (Thyroglobulin) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-raf) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Animals MH - Cell Line MH - Cell Proliferation/*drug effects MH - Culture Media, Serum-Free/pharmacology MH - DNA Replication/drug effects MH - Enzyme Activation MH - Extracellular Signal-Regulated MAP Kinases/*biosynthesis MH - Flavonoids/pharmacology MH - Gene Expression/drug effects MH - Insulin/pharmacology MH - MAP Kinase Kinase Kinases/*biosynthesis MH - Protein Kinase Inhibitors/pharmacology MH - Proto-Oncogene Proteins c-fos/metabolism MH - Proto-Oncogene Proteins c-jun/metabolism MH - Proto-Oncogene Proteins c-myc/metabolism MH - Proto-Oncogene Proteins c-raf/*biosynthesis MH - Rats MH - Thyroglobulin/*pharmacology MH - Thyroid Gland/cytology/*drug effects/enzymology MH - Thyrotropin/pharmacology EDAT- 2012/03/27 06:00 MHDA- 2012/06/02 06:00 CRDT- 2012/03/27 06:00 PHST- 2012/03/08 00:00 [received] PHST- 2012/03/09 00:00 [accepted] PHST- 2012/03/27 06:00 [entrez] PHST- 2012/03/27 06:00 [pubmed] PHST- 2012/06/02 06:00 [medline] AID - S0006-291X(12)00493-7 [pii] AID - 10.1016/j.bbrc.2012.03.046 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2012 Apr 13;420(3):611-5. doi: 10.1016/j.bbrc.2012.03.046. Epub 2012 Mar 16.