title: Nuclear factor-kappaB-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53.
abstract: KAI1/CD82 has been shown to be a metastasis suppressor for several human cancers, and a recent study revealed that wild-type tumor suppressor p53 can directly activate KAI1/CD82 gene expression. However, the response of KAI1/CD82 expression in cancer cells to exogenous stimulants has not been investigated. The present study examined whether tumor necrosis factor (TNF), which mediates many of the cellular responses associated with inflammatory reactions or cancer progression, can affect the KAI1/CD82 expression in lung cancer cells and, if so, whether nuclear factor (NF)-kappaB, a key molecule in TNF-mediated gene expression, is involved in the mechanism of KAI1/CD82 induction. Our results demonstrated that expression of KAI1/CD82 in PC-14 cells expressing mutant p53 could be augmented by TNF-alpha, and that transfer of the gene for a specific inhibitor of NF-kappaB, IkappaB alphaSR (mutant IkappaB alpha; NF-kappaB super-repressor), into PC-14 cells could inhibit this augmentation. The amount of NF-kappaB in the nucleus of PC-14/IkappaB alphaSR cells correlated well with KAI1/CD82 mRNA and protein expression. In addition, IkappaB alphaSR gene transfer inhibited the spontaneous expression of KAI1/CD82 protein in KAI1/CD82-high-expressing RERF-LC-OK cells, which contain a mutant-type p53. These observations indicate that NF-kappaB activation may play a role in the regulation of KAI1/CD82 expression in lung cancer cells independently of wild-type p53, and suggest that KAI1/CD82 expression may be regulated by interaction with the host microenvironment.
authors.affiliation: Third Department of Internal Medicine, The University of Tokushima School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shinohara
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: N
authors.initials: N
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Nokihara
authors.forename: H
authors.initials: H
authors.lastname: Hamada
authors.forename: N
authors.initials: N
authors.lastname: Mukaida
authors.forename: S
authors.initials: S
authors.lastname: Sone
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins; D051861:Kangai-1 Protein; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011759:Pyrrolidines / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013859:Thiocarbamates / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015703:Antigens, CD; C497688:CD82 protein, human; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011518:Proto-Oncogene Proteins; D011759:Pyrrolidines; D012334:RNA, Neoplasm; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D000072000:NF-KappaB Inhibitor alpha; C020972:pyrrolidine dithiocarbamic acid