Downregulation of wild-type beta-catenin expression by interleukin 6 in human hepatocarcinoma HepG2 cells: a possible role in the growth-regulatory effects of the cytokine?
We investigated the antitumour effects of interleukin 6 (IL-6) on hepatocarcinoma HepG2 cells, endowed with high levels of a mutated, non-degradable, beta-catenin. IL-6 produced minimal growth-inhibitory effects and no apoptosis or gross changes in cell adhesion. Interestingly, however, it caused a consistent decrease in the cytoplasmic levels of wild-type, but not of mutated, beta-catenin protein. There was no effect on E-cadherin or gamma-catenin and a reduction in alpha-catenin occurred only at high concentrations. IL-4, a non-related cytokine, did not modify the content of beta-catenin. IL-6 did not influence beta-catenin mRNA levels. LiCl, a potent inhibitor of Glycogen Synthase Kinase 3beta (GSK3beta) activity, abrogated the IL-6-induced inhibition of wild-type beta-catenin. This indicates that IL-6 can affect wild-type beta-catenin through a post-transcriptional mechanism, probably involving degradation of the protein. This effect might be related to the growth-regulatory activities of IL-6 in other situations, but can not counteract the oncogenic expression of mutated beta-catenin in HepG2 cells or possibly in other tumour cells with similar gene mutations.
Institute of Developmental Biology, C.N.R., Via Ugo La Malfa 153, 90146, Palermo, Italy.
M
M
Cervello
M
M
Notarbartolo
M
M
Landino
A
A
Cusimano
L
L
Virruso
G
G
Montalto
N
N
D'Alessandro
D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators; D014407:Tumor Cells, Cultured / Q000187:drug effects; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin