title: Heat shock protein 20 (HSPB6) regulates TNF-α-induced intracellular signaling pathway in human hepatocellular carcinoma cells.
abstract: We previously demonstrated that the expression of HSP20, a small heat shock protein, is inversely correlated with the progression of HCC. Inflammation is associated with HCC, and numerous cytokines, including TNF-α, act as key mediators in the progression of HCC. In the present study, we investigated whether HSP20 is implicated in the TNF-α-stimulated intracellular signaling in HCC using human HCC-derived HuH7 cells in the presence of TNF-α. In HSP20-overexpressing HCC cells, the cell growth was retarded compared with that in the control cells under long-term exposure of TNF-α. Because NF-κB pathway is the main intracellular signaling system activated by TNF-α, we investigated the effects of HSP20-overexpression of this pathway. The protein levels of IKK-α, but not IKK-β, in the HSP20-overexpressing cells were decreased. Short-term exposure to TNF-α-induced phosphorylation and degradation of IκB, and the phosphorylation and transactivational activity of NF-κB were suppressed in the HSP20-overexpressing HCC cells. Furthermore, the increase in IKK-α levels was accompanied by a decrease in the HSP20 levels in human HCC tissues. These findings strongly suggest that HSP20 might decrease the IKK-α protein level and that it down-regulates the TNF-α-stimulated intracellular signaling in HCC, thus resulting in the suppression of HCC progression.
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nagasawa
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan; Department of Radiological Technology, Suzuka University of Medical Science, Suzuka 513-8670, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Yasuda
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Matsuura
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.affiliation: Department of Surgery, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kaneoka
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. Electronic address: okozawa@gifu-u.ac.jp.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D050886:HSP20 Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D015398:Signal Transduction; D015533:Transcriptional Activation / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D050886:HSP20 Heat-Shock Proteins; C494382:HSPB6 protein, human; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha; C496559:CHUK protein, human; D051550:I-kappa B Kinase; C496560:IKBKB protein, human
keywords: Cell proliferation; HCC; HSP20; IKK-α; TNF-α