Expression of Epithelial Cadherin and α– and β–Catenins in Nontumoral Livers and Hepatocellular Carcinomas

Abstract

Expression of the cell adhesion molecule, epithelial nism. 2,3 The transmembrane linker glycoprotein that cadherin (E-CD) and its binding proteins, a-and b-caten-mediates this adhesion is thought to be epithelial cadins, in normal liver, chronic liver diseases, and hepato-herin (E-CD), the homophilic interaction of which links cellular carcinomas (HCCs) was investigated immuno-adjacent cells.4 E-CD is a member of the cadherin famhistologically. In normal liver, weak immunostaining of ily that is involved in Ca 2/ -dependent cell-cell adhesion E-CD and catenins was observed at the lateral mem-in vertebrate tissues.4,5 Regulated E-CD expression fabranes of the hepatocytes, whereas at the interlobular cilitates several epithelial morphogenetic events, in- 3,4 In rat livers, it is suggested that Eas well as Hering canals and proliferating ductules, CD may be a fundamental factor in hepatocyte polarity showed markedly increased molecular expression. Anal-formation and in shaping hepatic plates during embryysis of 66 HCC lesions revealed that the majority (64.3-onic development.6 However, the physiological roles 96.6%) of thin trabecular-and pseudoglandular-type tu-and distribution of E-CD in human liver are still poorly mors preserved or overexpressed E-CD and catenins, understood. whereas thick trabecular-type HCCs frequently showedRecent studies have shown that the full adhesive low E-CD and a-catenin expression (56.5-65.2% reducfunction of E-CD is expressed only when it is complexed tion), suggesting that the thick trabecular histology represented diffuse tumor cell growth. Likewise, the E-CD via a specific cytoplasmic binding domain with three and catenin expression levels correlated with the HCC cytosolic proteins, termed a-, b-, and g-catenins.7,8 Cacell differentiation grades. These collective results indi-tenins mediate connection of E-CD to the actin filament cate that intercellular adhesion mediated by the E-CD-network and link E-CD to other transmembrane procatenin system plays a role in morphological changes in teins, such as Na Furthermore, b-catenin was shown to be the common target for signal transduction pathways mediated by Tight cell-cell binding is an essential phenomenon the proto-oncogenes src and wnt-1 10 and for a-and bthat characterizes the epithelial cellular phenotype, catenins bound to a protein product of the tumor supwhich is achieved primarily by the adherens junctions pressor gene APC (adenomatous polyposis coli). 11,12 present on the cell membranes.1 In normal epithelium, These findings suggest that, in addition to regulating the junctions form a continuous adhesion belt around E-CD activity, catenins play a role in controlling tumoreach interacting cell; those in adjacent epithelial cells igenic cell growth. are directly apposed to them, and the interacting memIt has been known for some time that intercellular branes are held together by a Ca 2/ -dependent mechaadhesion becomes weakened morphologically in carcinomas. Indeed, certain types of carcinoma, such as signet ring cell and und...

PIN1 overexpression and β-catenin gene mutations are distinct oncogenic events in human hepatocellular carcinoma

“…b-catenin protein accumulation was detected in 21 of 32 (66%) and 42 of 60 (70%) tumors by Western blot analysis (Figure 1b), and immunohistochemistry (Figure 2c), respectively, which was comparable with the results from previous studies (Ihara et al, 1996;Huang et al, 1999). Nuclear staining pattern of b-catenin was detected in six cases, with the rest showing strong staining in the cytoplasm and/or cytoplasmic membrane.…”

“…Previous studies have shown that bcatenin is overexpressed in about 70% of HCC (Ihara et al, 1996;Huang et al, 1999), although only about 10-20% of these cases show b-catenin gene mutations (de La Coste et al, 1998;Miyoshi et al, 1998;Wong et al, 2001). Cyclin D1 gene amplification was reported in less than 15% of HCC patients (Zhang et al, 1993;Nishida et al, 1994), but overexpressions of cyclin D1 mRNA and cyclin D1 protein were reported in up to 22% (Nishida et al, 1994) and 58% (Joo et al, 2001) of HCC, respectively.…”

“…Somatic mutations of b-catenin have been shown to occur in approximately 10-20% of HCC (de La Coste et al, 1998;Miyoshi et al, 1998). However, the percentage of HCC with b-catenin protein accumulation is much higher, with immunohistochemical study showing b-catenin overexpression in 50-83% of HCCs (Ihara et al, 1996;Huang et al, 1999). AXIN1 and AXIN2 gene mutations are unlikely to contribute significantly, as these have only been reported in about 5-10% of HCC (Taniguchi et al, 2002).…”

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

“…[18][19][20][21][22][23][24][25][26] For example, Charpin et al 21 reported that down-regulation of E-cad expression was noted in a majority of breast carcinomas; this significantly correlated with tumor grade and expression of p53, MIB-1 (growth fraction) and c-erbB2 in breast carcinomas. In the liver, Ihara et al 29 reported that thin trabecular and pseudoglandular HCC preserved or overexpressed E-cad, ␣-catenin, and ␤-catenin, whereas thick trabecular HCC frequently showed low E-cad, ␣-catenin, and ␤-catenin expression. They also reported that the E-cad, ␣-catenin, and ␤-catenin expression levels correlated with HCC differentiation grades.…”

“…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.…”