Expression of cadherins and alpha-catenin in primary epithelial tumors of the liver

Kozyraki, Renata; Scoazec, J.Y.; Jf, Fléjou; d’Errico, Angelo; Bédossa, Pierre; Terris, Benoı̂t; Fiorentino, Michelangelo; Af, Bringuier; Grigioni, Francesco; Feldmann, Gérard

doi:10.1053/gast.1996.v110.pm8613003

Cited by 78 publications

(82 citation statements)

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“…In this regard, the expression or function of the cadherin-catenin complexes has been shown to be impaired in HCC and HCC-derived cell lines. Cadherin and a-catenin expression is frequently reduced in HCCs, correlating with tumor size, low grade of di erentiation and capsular and vascular invasion (Kozyraki et al, 1996). Deletion of the E-cadherin gene has been shown in HBV-positive HCCs (Slagle et al, 1993;Zondervan et al, 2000) and somatic mutations have been detected in the b-catenin gene in human HCCs and myc or ras transgenic mice (de La Coste et al, 1998;Nhieu et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner

et al. 2001

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Chronic hepatitis B virus infection is strongly associated with the development of hepatocellular carcinoma (HCC). Epithelial tumors are frequently characterized by loss of cadherin expression or function. Cadherindependent adhesion prevents the acquisition of a migratory and invasive phenotype, and loss of its function is itself enough for the progression from adenoma to carcinoma. The HBx protein of hepatitis B virus is thought to contribute to the development of the carcinoma, however, its role in the oncogenic and metastatic processes is far from being fully understood. We report herein the ability of HBx to disrupt intercellular adhesion in three di erent cell lines stably transfected with an inducible HBx expression vector. The linkage between the actin cytoskeleton and cadherin complex, which is essential for its function, is disrupted in the presence of HBx, as indicated by detergent solubility and immunoprecipitation experiments. In addition, b-catenin was tyrosine phosphorylated in HBx-expressing cells. Inhibition of the src family of tyrosine kinases resulted in the prevention of the disruption of adherens junctions. These results suggest that HBx is able to disrupt intercellular adhesion in a src-dependent manner, and provide a novel mechanism by which HBx may contribute to the development of HCC. Oncogene (2001) 20, 3323 ± 3331.

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Section: Discussionmentioning

confidence: 99%

The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner

et al. 2001

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“…E-cadherin deficiency in tumours would lead to changes in cell morphology and motility, so that E-cadherin is being considered to be a suppressor of cancer invasion [30]. In primary HCCs, E-cadherin expression is absent or reduced in amount as compared to normal liver tissues, which may be connected with intrahepatic metastasis of hepatocellular carcinoma [31], [32]. Another result of the reduced expression or inactivation E-cadherin gene may lie in the disruption of E-cadherin/ catenin complex and subsequently the releasing of the β-catenin into the cytoplasm in the course of hepato-carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-hetero- zygosity on chromosome 16q21-q23 and 9p21-p23

et al. 2000

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To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65 %), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49 %) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24 %) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/p16 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21-q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC.

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“…They also reported that the E-cad, ␣-catenin, and ␤-catenin expression levels correlated with HCC differentiation grades. 29 Kozyraki et al 32 reported that E-cad and ␣-catenin expression was frequently reduced or absent in HCC, and that alterations in cadherin expression in HCC correlated with large tumor size, low grade of histological differentiation, and occurrence of capsular and vascular invasion. The present study revealed for the first time that E-cad, ␣-catenin, and ␤-catenin expression was preserved (eu-regulation) or reduced (downregulation) relative to non-cancerous bile ducts in a majority of CC.…”

Section: Discussionmentioning

confidence: 99%

Expression of e-cadherin, α-catenin, β-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

et al. 1998

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Immunolocalization of E-cadherin (E-cad), ␣-catenin, ␤-catenin, and CD44 has rarely been investigated in human cholangiocarcinoma (CC). We, therefore, immunohistochemically examined the expression of E-cad, ␣-catenin, ␤-catenin, CD44 standard (CD44s), and CD44 variants (CD44v) including CD44v5, CD44v6, CD44v7-8, and CD44v10 in normal adult livers and in 47 cases of CC; and the results were then correlated with tumor grade, vascular invasion, metastasis, p53 expression, proliferative fraction (Ki-67 labeling), and c-erbB2 expression. In normal livers, E-cad, ␣-catenin and ␤-catenin, but not CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10, were expressed at the cell membrane of normal intrahepatic bile ducts. In CC, membranous expression of E-cad, ␣-catenin, and ␤-catenin was the same or reduced when compared with noncancerous bile ducts in the majority of CC. We found that the down-regulation of E-cad, ␣-catenin, and ␤-catenin expression significantly correlated with tumor high grade, but not with vascular invasion, metastasis, p53 expression, Ki-67 labeling, or c-erbB2 expression, except for ␤-catenin, the down-regulation of which was associated with c-erbB2 down-regulation. CD44s, CD44v5, CD44v6, CD44v7-8 and CD44v10 were frequently expressed at the membrane of CC cells. There were, however, no significant correlations between these aberrant CD44 expression and tumor grade, metastasis, vascular invasion, p53 expression, Ki-67 labeling, or c-erbB2 expression, with a few exceptions of CD44s and CD44v5. We found that CD44s aberrant expression significantly correlated with absence of metastasis and vascular invasion, and that CD44v5 aberrant expression significantly correlated with p53 under-expression. These results suggest that membranous expression of E-cad, ␣-catenin, and ␤-catenin is reduced in a majority of CC and this down-regulation correlates with CC high grade, and that ␤-catenin down-regulation is associated with c-erbB2 down-regulation. The data also suggested that CD44s, CD44v5, CD44v6, CD44v7-8, and CD44v10 may be neoexpressed during carcinogenesis of CC but this neoexpression does not correlate with tumor progression in CC, with the exception of CD44s and CD44v5. (HEPATOLOGY 1998;27:974-982.)

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Expression of cadherins and alpha-catenin in primary epithelial tumors of the liver

Cited by 78 publications

References 1 publication

The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner

The hepatitis B virus HBx protein induces adherens junction disruption in a src-dependent manner

Genetic aberration in primary hepatocellular carcinoma: correlation between p53 gene mutation and loss-of-hetero- zygosity on chromosome 16q21-q23 and 9p21-p23

Expression of e-cadherin, α-catenin, β-catenin, and CD44 (standard and variant isoforms) in human cholangiocarcinoma: An immunohistochemical study

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