Up-regulation of E-cadherin and I-catenin in human hepatocellular carcinoma cell lines by sodium butyrate and interferon-alpha.
Human E-cadherin is a homophilic cell adhesion molecule and its expression is well preserved in normal human hepatocytes; a decrease in its expression has been observed in poorly differentiated hepatocellular carcinoma cells. We examined the alteration of E-cadherin and catenin expressions caused by differentiation inducers in human hepatocellular carcinoma cells. Hepatocellular carcinoma cell lines, HCC-T and HCC-M, were cultured with all-trans retinoic acid (ATRA), dexamethasone (DEX), sodium butyrate, and interferon-alpha. E-cadherin expression was only up-regulated by butyrate and interferon-alpha (IFN-alpha) in both cell lines, studied by means of fluorescence immunostaining and flow cytometry. The localization of E-cadherin staining was shown at their cell membrane. According to the increase in E-cadherin expression, beta-catenin expression appeared at the cell membrane of both cell lines when treated with butyrate and IFN-alpha. Such an appearance was not observed when cells were treated with ATRA and DEX. Western blotting showed that alpha- and y-catenin expression was not changed, while only the expression of beta-catenin increased. Beta-catenin oncogenic activation as a result of amino acid substitutions or interstitial deletions within or including parts of exon 3, which has been demonstrated recently, was not detected in these cell lines by direct deoxyribonucleic acid sequencing. These results suggest that the expression and interaction between E-cadherin and wild-type beta-catenin are potentially modulated by butyrate and IFN-alpha, and that these two agents are potent inhibitors of hepatocellular carcinoma cell invasion and metastasis.
Masuda
T
T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Saito
H
H
Kaneko
F
F
Atsukawa
K
K
Morita
M
M
Inagaki
H
H
Kumagai
N
N
Tsuchimoto
K
K
Ishii
A H
AH
D019943:Amino Acid Substitution; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology*; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D002462:Cell Membrane / Q000737:chemistry; D003470:Culture Media; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D015534:Trans-Activators; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051176:beta Catenin
D002087:Butyrates; C495270:CTNNB1 protein, human; D015820:Cadherins; D003470:Culture Media; D003598:Cytoskeletal Proteins; D016898:Interferon-alpha; D015534:Trans-Activators; D051176:beta Catenin; D014212:Tretinoin; D003907:Dexamethasone