title: Role of a novel CAR-induced gene, TUBA8, in hepatocellular carcinoma cell lines.
abstract: Phenobarbital (PB), a nongenotoxic carcinogen, activates the nuclear constitutive active/androstane receptor (CAR), resulting in the transcriptional induction or repression of various hepatic genes. We previously demonstrated that liver tumors developed after chronic PB treatment only when CAR is present. To understand the molecular mechanism of tumor promotion, cDNA microarray analysis was performed. We identified tubulin alpha 8 (TUBA8) as one of the candidate genes that may be involved in liver tumor promotion. Tuba8 mRNA was induced with PB treatment in mouse livers before tumor development as well as in tumor tissues. Because the functions of TUBA8 are unknown in liver, we investigated the effects of TUBA8 gene expression on cell growth, proliferation, and cell migration. Sense or antisense cDNA for Tuba8 was stably transfected into Huh7 and HepG2 cells. Exogenous overexpression of Tuba8 inhibited cell growth and proliferation in Huh7 but not in HepG2 cells, while cell migration was increased in HepG2 cells but not Huh7 cells. These results indicate that TUBA8 can play a role in the regulation of cell growth, proliferation, and cell migration in a cell-specific manner in vitro, suggesting that TUBA8 may contribute to mouse liver tumorigenesis through these functions.
authors.affiliation: Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kamino
authors.forename: Rick
authors.initials: R
authors.lastname: Moore
authors.forename: Masahiko
authors.initials: M
authors.lastname: Negishi
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D000090702:Constitutive Androstane Receptor; D005434:Flow Cytometry; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010634:Phenobarbital / Q000633:toxicity; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014158:Transcription, Genetic; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000090702:Constitutive Androstane Receptor; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C408046:TUBA8 protein, human; C501978:Tuba8 protein, mouse; D014404:Tubulin; D010634:Phenobarbital