A novel amplification target, DUSP26, promotes anaplastic thyroid cancer cell growth by inhibiting p38 MAPK activity.
Anaplastic thyroid cancer (ATC) is one of the most lethal of all human tumors, but cytogenetic information concerning ATC is extremely limited. Using our in-house array-based comparative genomic hybridization and 14 ATC cell lines with further fluorescence in situ hybridization analysis, we demonstrated amplification of the DUSP26 gene, known by another report as MAP kinase phosphatase-8. DUSP26 was overexpressed in ATC cell lines and primary ATC tumor samples. When overexpressed, either exogenously or endogenously, DUSP26 promoted growth of the ATC cells. DUSP26 encodes a protein containing a dual-specificity phosphatase domain that can dephosphorylate itself. DUSP26 effectively dephosphorylates p38 and has a little effect on extracellular signal-regulated kinase in ATC cells. DUSP26 protein formed a physical complex with p38, and promoted survival of ATC cells by inhibiting p38-mediated apoptosis. Our findings suggest that DUSP26 may act as an oncogene in ATC, and might be a useful diagnostic marker and therapeutic target of this disease.
Yu
W
W
Department of Molecular Cytogenetics, Medical Research Institute and Graduate School of Biomedical Science, Tokyo, Japan.
Imoto
I
I
Inoue
J
J
Onda
M
M
Emi
M
M
Inazawa
J
J
D017209:Apoptosis / Q000235:genetics; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003001:Cloning, Molecular; D054637:Dual-Specificity Phosphatases; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D054639:Mitogen-Activated Protein Kinase Phosphatases; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism
D034741:RNA, Small Interfering; D048051:p38 Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C500883:DUSP26 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases; D053148:Caspase 3