Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E-Cadherin has been shown to be an invasion tumor suppressor gene, but few epidemiological studies have revealed relationships between loss of E-cadherin expression and invasive tumor growth and/or metastasis. The adhesive function of E-cadherin is dependent on the integrity of the catenin components which link E-cadherin to the actin filaments. In order to achieve a better correlation between the loss of cell adhesion and metastasis in cancer, we decided to investigate both E-cadherin and the catenins. 157 archival primary mammary carcinomas were immunohistochemically studied using antibodies against E-cadherin, alpha-, beta- and gamma-catenin. The following results were obtained: (a) Independent of the presence of E-cadherin, loss of expression of one or multiple catenins was noted; (b) loss of E-cadherin and alpha-catenin expression was more pronounced in lobular-type than ductal-type carcinomas; c) axillary lymph node metastases were completely lacking only in the group where expression of E-cadherin, alpha- and beta- catenin was preserved: d) no correlation between expression of c-erbB-2 and E-cadherin or one of the catenins was found. The results demonstrate for the first time that consideration of both the expression of E-cadherin and of the three catenins is useful in evaluation of the metastatic potential of mammary carcinomas.
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PMID:Expression of E-cadherin and catenins in invasive mammary carcinomas. 906 80

Over-expression of epidermal growth factor receptor (EGFR) in ovarian cancer has been well documented. Human NIH:OVCAR-8 ovarian carcinoma cells were transfected with an expression vector containing the anti-sense orientation of truncated human EGFR cDNA. EGFR anti-sense over-expression resulted in decreased EGFR protein and mRNA expression, cell proliferation and tumor formation in nude mice. In accordance with the reduced levels of EGFR in EGFR anti-sense-expressing cells, tyrosine phosphorylation of EGFR was decreased compared to untransfected parental cells treated with EGF. In EGFR anti-sense-transfected cells, expression of erbB-3, but not erbB-2, was increased. In addition, basal and heregulin-beta 1-stimulated tyrosine phosphorylation of erbB-3 was higher in EGFR anti-sense vector-transfected cells. A morphological alteration in EGFR anti-sense gene-expressing cells was correlated with a decrease in the expression of E-cadherin, alpha-catenin and, to a lesser extent, beta-catenin. Changes in the expression of these proteins were associated with a reduction in complex formation among E-cadherin, beta-catenin and alpha-catenin and between beta-catenin and EGFR in EGFR anti-sense-expressing cells compared to sense-transfected control cells. These results demonstrate that EGFR expression in ovarian carcinoma cells regulates expression of cell adhesion proteins that may enhance cell growth and invasiveness.
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PMID:Anti-sense suppression of epidermal growth factor receptor expression alters cellular proliferation, cell-adhesion and tumorigenicity in ovarian cancer cells. 1105 72

Special attention has focused on E-cadherin and the invasiveness of breast carcinoma because E-cadherin was suggested to be the major cell adhesion molecule in the mammary gland. In the cytoplasm, E-cadherin is linked to beta-catenin and alpha-catenin which mediate the connection of the cytoskeleton. In addition, c-erbB-2 oncoprotein causes disruption of this cell adhesion system through beta-catenin phosphorylation. We investigated the expression of E-cadherin, alpha-catenin and c-erbB-2 gene products in 66 invasive ductal carcinomas by immuno-histochemistry to examine the relation between the E-cadherin mediated cell adhesion system and histological subtypes used in Japan as well as histological grading. The series included 21 papillotubular carcinomas, 16 solid-tubular carcinomas and 29 scirrhous carcinoma. There were 33 cases of grade I, 20 cases of grade II and 13 cases of grade III. We defined P&P&N as E-cadherin positive and alpha-catenin positive and c-erbB-2 negative cases to evaluate the preservation of the E-cadherin mediated cell adhesion system. There were only 13 cases (19.7%) of P&P&N in total. As for the frequency of E-cadherin/alpha-catenin/c-erbB-2 expression and P&P&N, no significant difference between histological subtypes was found. However, those in the grade I group tended to be higher than in the other two grade groups. Regarding the rates of alpha-catenin positive cases and P&P&N cases, there were significant differences between the grade I group and a combination group consisting of the grade II and grade III groups. These results suggest that the E-cadherin-mediated cell adhesion system is frequently lost in invasive ductal-type breast cancers by random loss of E-cadherin/catenins or c-erbB-2 overexpression, and that the preservation of this system correlates with well differentiated morphological features.
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PMID:Expression of E-cadherin catenin and C-erbB-2 gene products in invasive ductal-type breast carcinomas. 1206 29

E-cadherin function leads to the density-dependent contact inhibition of cell growth. Because cadherins control the overall state of cell contact, cytoskeletal organization, and the establishment of many other kinds of cell interactions, it remains unknown whether E-cadherin directly transduces growth inhibitory signals. To address this question, we have selectively formed E-cadherin homophilic bonds at the cell surface of isolated epithelial cells by using functionally active recombinant E-cadherin protein attached to microspheres. We find that E-cadherin ligation alone reduces the frequency of cells entering the S phase, demonstrating that E-cadherin ligation directly transduces growth inhibitory signals. E-cadherin binding to beta-catenin is required for cell growth inhibition, but beta-catenin/T-cell factor transcriptional activity is not involved in growth inhibition resulting from homophilic binding. Neither E-cadherin binding to p120-catenin nor beta-catenin binding to alpha-catenin, and thereby the actin cytoskeleton, is required for growth inhibition. E-cadherin ligation also inhibits epidermal growth factor (EGF) receptor-mediated growth signaling by a beta-catenin-dependent mechanism. It does not affect EGF receptor autophosphorylation or activation of ERK, but it inhibits transphosphorylation of Tyr845 and activation of signal transducers and activators of transcription 5. Thus, E-cadherin homophilic binding independent of other cell contacts directly transduces growth inhibition by a beta-catenin-dependent mechanism that inhibits selective signaling functions of growth factor receptors.
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PMID:E-cadherin homophilic ligation inhibits cell growth and epidermal growth factor receptor signaling independently of other cell interactions. 1739 17

Tyrosine phosphorylation of beta-catenin, an intracytoplasmic cadherin-binding protein, causes disruption of the cadherin-mediated cell adhesion system in cancer cells. We identified that the c-erbB-2 protein activated by TGFalpha was capable of binding to the 12th armadillo repeat (arm12) of beta-catenin with increased phosphorylation-state level. We produced a monoclonal antibody, 4G7, which recognizes a phosphorylated-tyrosine residue (Tyr-654) located at arm12 of beta-catenin. Tyrosine phosphorylation of the arm12 was detected after stimulation with TGFalpha in TMK-1. Immunoprecipitation analyses using 4G7, anti-beta-catenin, alpha-catenin, the c-erbB-2 gene product and phosphotyrosine antibodies indicated that tyrosine phosphorylation of the arm12 was closely correlated with dissociation between E-cadherin/beta-catenin and alpha-catenin or the c-erbB-2 gene product, but not with dissociation between beta-catenin and E-cadherin. Immunocytochemical staining of TMK-1 cells using the 4G7 antibody revealed that tyrosine phosphorylation of the arm12 was localized at cell-cell contact sites of cancer cells transiently and only after TGFalpha treatment. Immunohistochemical localization of the 4G7 antibody was observed in cancer cells at the invasive front where they detached from cancer nests. These findings indicated that the tyrosine phosphorylation of arm12 is a key marker of cadherin dysfunction and the 4G7 antibody may be useful in screening for a beta-catenin phosphorylation ligand or tyrosine kinases.
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PMID:Tyrosine-phosphorylation of the 12th armadillo-repeat of beta-catenin is associated with cadherin dysfunction in human cancer. 1963 72

Expression of E-cadherin, alpha-, beta- and gamma-catenins were studied in 100 patients with primary breast cancer compiled of 57 invasive ductal carcinomas (IDC) and 43 invasive lobular carcinomas (ILC) by means of immunohistochemistry. Loss of E-cadherin was observed in 26 (45.6%), and alpha-, beta- and gamma-catenin expression was lacking in 22 (38.6%), 27 (47.4%) and 22 (38.6%) IDCs, respectively. The expression in ILCs was significantly lower, as compared to IDCs (p<0.001). Immunostaining of both E-cadherin and catenins was completely lacking in 27 (47.4%) IDCs and 30 (93.8%) ILCs. Go-expression of E-cadherin/beta-catenin or E-cadherin/gamma-catenin was preserved more frequently than that of E-cadherin/alpha-catenin complexes. E-cadherin/catenin complex expression showed significant positive correlation with histological differentiation (p=0.037), ER (p=0.017) and PR expression (p=0.052), and negative correlation with c-erbB-2 receptor overexpression (p=0.046). Patients with tumours showing adhesion complexes containing alpha-catenin had an increased overall survival rate compared to other patients. Expression of either E-cadherin or alpha-catenin only, without the formation of entire adhesion complexes, was not correlated with overall survival. Thus, determination of both E-cadherin and catenins is suggested to add further information to estimate the prognosis of breast cancer patients.
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PMID:Expression of E-cadherin/catenin complexes in breast cancer. 2152 42