Apg-2 has a chaperone-like activity similar to Hsp110 and is overexpressed in hepatocellular carcinomas.
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. We constructed subtracted cDNA libraries enriched with genes overexpressed in HCCs. Among the 17 genes identified were molecular chaperones, Hsp110, Hsp90B, and Hsp70-1. Expression of the Hsp110 family members was further analyzed, and increased transcript levels of Hsp110 and Apg-2, but not Apg-1, were found in 12 and 14, respectively, of 18 HCCs. Immunohistochemical analysis demonstrated the overexpression of the proteins in tumor cells. Apg-2 had chaperone ability similar to Hsp110 in a thermal denaturation assay using luciferase, and showed anti-apoptotic activity. These results suggest that the Hsp110 family members play important roles in hepatocarcinogenesis through their chaperoning activities.
Department of Clinical Molecular Biology, Faculty of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Kazuhisa
K
Gotoh
Kohsuke
K
Nonoguchi
Hiroaki
H
Higashitsuji
Yoshiyuki
Y
Kaneko
Toshiharu
T
Sakurai
Yasuhiko
Y
Sumitomo
Katsuhiko
K
Itoh
John R
JR
Subjeck
Jun
J
Fujita
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001681:Biological Assay; D019556:COS Cells; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002522:Chlorocebus aethiops; D002999:Clone Cells; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins; D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics*; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D011489:Protein Denaturation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D050957:HSP110 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C121993:HSPA4 protein, human; D006360:Heat-Shock Proteins; C485680:Hspa4 protein, mouse; D008164:Luminescent Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D008156:Luciferases