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Prognostic and clinicopathological features of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D1 expression in human esophageal squamous cell carcinoma.

AIM: To investigate the expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) in patients with esophageal squamous cell carcinoma (ESCC), and analyze their interrelationship with clinicopathological variables and their effects on prognosis. METHODS: Expression of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin and cyclin D(1) was determined by EnVision or SABC immunohistochemical technique in patients with ESCC consecutively, their correlation with clinical characteristics was evaluated and analyzed by univariate analysis. RESULTS: The reduced expression rate of E-cadherin, alpha-catenin, beta-catenin and gamma-catenin was 88.7%, 69.4%, 35.5% and 53.2%, respectively. Cyclin D1 positive expression rate was 56.5%. Expression of gamma-catenin was inversely correlated with the degree of tumor differentiation and lymph node metastasis (chi(2) = 4.183 and chi(2) = 5.035, respectively, P<0.05), whereas the expression of E-cadherin was correlated only with the degree of differentiation (chi(2) = 5.769, P<0.05). Reduced expression of E-cadherin and gamma-catenin was associated with poor differentiation of tumor, reduced expression of gamma-catenin was also associated with lymph node metastasis. There obviously existed an inverse correlation between level of E-cadherin and gamma-catenin protein and survival. The 3-year survival rates were 100% and 56% in E-cadherin preserved expression group and in reduced expression one and were 78% and 48% in gamma-catenin preserved expression group and in reduced expression one, respectively. The differences were both statistically significant. Correlation analysis showed the expression level of alpha-catenin correlated with that of E-cadherin and beta-catenin (P<0.05). CONCLUSION: The reduced expression of E-cadherin and gamma-catenin, but not alpha-catenin, beta-catenin and cyclin D1, implies more aggressive malignant behaviors of esophageal carcinoma cells and predicts the poor prognosis of patients.

Biomarkers, Tumor↗

Immunohistochemical analysis of E-cadherin, alpha-catenin, beta-catenin, gamma-catenin, and neural cell adhesion molecule (NCAM) in chordoma.

AIMS: The epithelioid features seen in chordoma are unique among mesenchymal tumours. However, no detailed analysis regarding cell-cell communication has been conducted in this epithelioid tumour. The aims of this study were to investigate cell-cell communication in chordoma. METHODS: By means of immunohistochemical techniques that incorporated a panel of monoclonal antibodies against cell adhesion molecules (CAMs), including E-cadherin, alpha-catenin, beta-catenin, gamma-catenin, and neural cell adhesion molecule (NCAM), the expression of CAMs was studied in 15 specimens of chordoma and eight specimens of chondrosarcoma. RESULTS: Most chordoma specimens showed some positive immunoreactivity for all the CAMs examined. For the various CAMs investigated, between two and five cases showed diffuse immunoreactions, indicating well preserved expression. Well preserved expression of all the CAMs examined was limited to only one case, thus indicating that the expression of CAMs was decreased in most of the chordoma specimens; however, no significant correlation was found between the decreased expression of CAMs and the histological grade of malignancy, cellular growth pattern, or clinical parameters in chordoma. In chondrosarcoma, only a few specimens showed positive immunoreactivity for CAMs and the expression of E-cadherin, beta-catenin, gamma-catenin, and NCAM was seen more frequently in the chordoma specimens than in the chondrosarcoma specimens. CONCLUSIONS: These results suggest that the expression of CAMs is associated with the formation and maintenance of chordoma tissue architecture, just as it is in other epithelial tumours or normal tissue. Immunohistochemistry for CAMs was found to be of diagnostic value for discriminating chordoma from chondrosarcoma, and these markers could be used along with the cytokeratins, which are already used for this purpose.

Adult↗

Indomethacin induces differential expression of beta-catenin, gamma-catenin and T-cell factor target genes in human colorectal cancer cells.

Indomethacin-induced G(1) arrest and apoptosis of human colorectal cancer (CRC) cells is associated with a dose-dependent decrease in beta-catenin protein levels. Beta-catenin plays a pivotal role in the WNT signalling pathway and its expression is frequently dysregulated at early stages of colorectal carcinogenesis. The objective of this study was to investigate the effect of indomethacin on catenin expression and downstream WNT signalling events in human CRC cells. Beta-catenin, gamma-catenin and T-cell factor (TCF) target gene (cyclin D1, c-MYC and PPARdelta) expression was studied following indomethacin treatment of SW480 and HCT116 cells. Cyclin D1 was used as a model TCF target gene for analysis of beta-catenin-TCF-4 DNA binding and trans-activation. Indomethacin treatment was associated with a specific decrease in beta-catenin (but not gamma-catenin) expression. Resulting TCF target gene expression was gene specific (cyclin D1, decreased; c-MYC, increased; PPARdelta, no significant change). Cyclin D1 promoter analysis revealed that indomethacin disrupted formation of a beta-catenin-TCF-4-DNA complex. Indomethacin-induced G(1) arrest and apoptosis is associated with specific beta-catenin down-regulation in human CRC cells in vitro. Differential expression of TCF target genes following indomethacin treatment implies complex effects on multiple genes which play an important role in colorectal carcinogenesis.

Acetylcysteine↗

Distinct location and prevalence of alpha-, beta-catenins and gamma-catenin/plakoglobin in developing and denervated skeletal muscle.

We studied the distribution of alpha-catenin, beta-catenin and gamma-catenin/plakoglobin in developing, adult and denervated mouse skeletal muscle. During primary myogenesis, all three catenins present a subsarcolemmal distribution within primary myotubes. During secondary myogenesis they accumulate at myotube-myotube contacts. In contrast to the other catenins, gamma-catenin is strongly expressed in the sarcoplasm. In adult muscle, all three catenins are localized on the presynaptic elements of the neuromuscular junction. In denervated muscles, alpha- and beta-catenins are upregulated like N- and M-cadherin, while the levels of gamma-catenin/plakoglobin remain unchanged. The developmental changes in localization and regulation of alpha- and beta-catenins in muscle compared to gamma-catenin/plakoglobin are suggestive of a privileged association of alpha- and beta-catenins with N- and M-cadherins, while gamma-catenin/plakoglobin appears to be expressed quite independently and must assume a different role during myogenesis.

Animals↗

Immunoreactive E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin proteins in hepatocellular carcinoma: relationships with tumor grade, clinicopathologic parameters, and patients' survival.

We evaluated the immunohistochemical expression status of E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin, and the relationship with tumor grade, clinicopathologic parameters, and patients' survival, in 107 surgically resected hepatocellular carcinoma (HCC), using a semiquantitative scoring system. These molecules were largely located at the cell membrane of HCC cells. Compared with expression in nontumorous liver, E-cadherin showed underexpression, whereas alpha-, beta-, and gamma-catenins showed overexpression in most HCC. E-cadherin expression significantly correlated inversely with HCC histological grade, being the highest in well-differentiated HCC. In contrast, alpha-, beta-, and gamma-catenins' expression significantly correlated positively with HCC grade, being the highest in poorly differentiated HCC. Significant positive correlations were found between gamma-catenin high expression and capsular invasion or presence of satellite nodules, and between beta-catenin high expression and vascular invasion. Kaplan-Meier examination of patients' survival indicated that HCC patients with underexpression of E-cadherin, alpha-catenin, and gamma-catenin, and patients with overexpression of beta-catenin, had poor survival rates. These results suggest that E-cadherin is downregulated while the 3 catenins are upregulated in HCC, that E-cadherin expression inversely correlates with HCC grade while the 3 catenins' expression positively correlates with HCC grade, and that HCC patients with downregulation of E-cadherin, alpha-catenin, and gamma-catenin and HCC patients with upregulation of beta-catenin have poor prognosis.

Adolescent↗

Proteolytic processing of the adherens junctions components beta-catenin and gamma-catenin/plakoglobin during apoptosis.

Apoptotic cells undergo specific morphological changes that include loss of cell-cell interactions. Cellular adhesiveness is dependent on members of the cadherin family of adhesion receptors and on the cytoplasmic adaptor proteins alpha-catenin, beta-catenin and gamma-catenin/plakoglobin. The caspase family of cystein proteases play a key role during the execution phase of the apoptotic program. These proteolytic enzymes, once activated, cleave cellular proteins which are important for the maintenance of cell integrity. Here we report that gamma-catenin is cleaved at different sites during apoptosis in various cell lines. The major apoptotic product of gamma-catenin still retains the ability to bind alpha-catenin but loses the carboxy-terminal region. We also show that gamma-catenin is cleaved by caspase-3 in vitro although with lower affinity when compared to PARP or beta-catenin. These findings indicate that multiple proteolytic events regulate the dismantling of the cell-cell junctional complexes during apoptosis.

Animals↗

[Correlation of E-cadherin, beta-catenin and gamma-catenin gene expression with the invasion and metastasis of gastric carcinoma].

OBJECTIVE: To study the association of the expressions of E-cadherin, beta;- and gamma-catenins in gastric carcinoma tissues with the invasion and metastasis of the tumor. METHODS: From 60 patients with gastric carcinoma, the paraffin-embedded specimens including 60 carcinoma tissues, 20 precancerous lesions (10 intestinal metaplasia and 10 dysplasia specimens) and 20 corresponding normal tissues adjacent to the carcinomas were obtained for detecting E-cadherin, beta;- and gamma-catenin expressions by immunohistochemistry. RESULTS: Positive staining for E-cadherin, beta- and gamma-catenins was clearly observed on the cellular membrane throughout the epithelium in all the normal and metaplastic gastric mucosa. In 1 out of the 10 specimens of dysplastic mucosa, the staining for E-cadherin and beta;-catenin was absent but gamma-catenin staining appeared normal. Up to 80% (48/60) of the gastric carcinoma specimens presented abnormal staining for at least one of the components of the cadherin- catenin complex, showing a close correlation to Ming's classification, TNM staging and lymph node metastasis (P<0.05). The rates of abnormal expression were 6.67% for E-cadherin, 55% for beta;-catenin and 58.33% for gamma-catenin. CONCLUSIONS: Abnormal expression of E-cadherin, beta;- and gamma-catenins results in loss of epithelial cell-to-cell adhesion, with leads to uncontrolled cell growth, and may therefore participate in malignant transformation of the cells, and closely associates with the invasive growth and metastasis of human gastric carcinoma.

Cadherins↗

Expression of adhesion proteins E-cadherin, alpha-catenin, beta-catenin and gamma-catenin is different in T1 and T2 breast tumours.

BACKGROUND: Breast cancer is the most common malignancy in women. Although an increasing number of patients with breast cancer are being cured by surgery, a considerable number of patients suffer relapse in the form of metastases after surgery. E-cadherin and catenins have documented roles in breast cancer progression. Mammography is supposed to decrease breast cancer mortality by detecting tumours while they are small and before they have reached a clinically detectable stage. AIM: In the present study, we wanted to evaluate whether there are differences in expression patterns of adhesion proteins, shown to be crucial in the metastatic process, between small tumours detected by mammography and clinically detected large tumours. METHODS: Expression of E-cadherin, alpha-catenin, beta-catenin and gamma-catenin was analysed using immunohistochemistry methods in 86 invasive breast carcinomas detected by mammography and compared with 90 clinically palpable invasive breast carcinomas. RESULTS: In the group of tumours detected by mammography (86 samples), reduced expression of E-cadherin was observed in 12 (14%) samples. Reduced expression of alpha-catenin was observed in four (4.6%) samples, and three (3.5%) samples showed reduced expression of beta-catenin. All samples showed strong expression of gamma-catenin. When expression patterns of these proteins were evaluated in 90 clinically detected tumours, we observed reduced expression of E-cadherin in 58 (64.4%) samples, 12 (13.3%) samples showed reduced expression of alpha-catenin, while nine (10%) samples showed reduced expression of beta-catenin. Strong expression of gamma-catenin was detected in all tumours also in this group.Statistical analyses revealed a highly significant difference in expression of E-cadherin (p<0.001). However, no statistically significant differences were observed in expression of alpha-catenin (p = 0.081) and beta-catenin (p = 0.092) between the two groups of tumours. CONCLUSION: Results indicate that T1 breast tumours harbour less alterations in E-cadherin-catenin complexes and therefore are probably less likely to disseminate, and patients probably have a better prognosis than if tumours are diagnosed as T2.

Aged↗

Expression of beta-catenin and gamma-catenin in epithelial tumor cell lines and characterization of a unique cell line.

In addition to its structural role, beta-catenin has recently been identified as an oncogene, while its homologue gamma-catenin (plakoglobin) seems to suppress tumorigenicity. Twenty-five epithelial tumor cell lines were screened; 18 expressed both beta- and gamma-catenin, two expressed neither protein, four showed beta- but not gamma-catenin expression, while only one cell line showed gamma- but not beta-catenin expression. As per literature search, the cell line expressing gamma- but not beta-catenin appeared to be unique. This cell line, SKBR-3, is a human breast cancer cell line which does not express beta-catenin or E-cadherin protein. There is, however, expression of beta-catenin, but not E-cadherin, mRNA. In order to determine the mechanism for this unique expression pattern, SKBR-3 cells were transfected with E-cadherin which resulted in expression of beta-catenin protein. Immunofluorescent staining of the E-cadherin transfected SKBR-3 cells revealed beta-catenin in the adherens junctions while transfection with just an epitope tagged (VSV) beta-catenin showed expression only in the nucleus. Double transfection with E-cadherin and VSV beta-catenin showed the beta-catenin in the adherens junction of the E-cadherin transfected cells. These results indicate that the mechanism for the lack of beta-catenin expression in the SKBR-3 cell line is possibly post-translational degradation and that when E-cadherin is transfected into these cells, the beta-catenin is stabilized in the adherens junction and not degraded. This cell line should be of interest to those studying the role of the homologues, beta- and gamma-catenin, in cancer pathogenesis.

Cell Adhesion Molecules↗

Expression of non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 in relation to patient outcome in human colon adenocarcinomas.

Non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 are key participants in the Wnt cell signalling pathway, in which aberrancies have been associated with malignant cell transformation. We assessed the independent prognostic value of these proteins in a clinical material. Tumours from a series of 162 patients operated on for Dukes' stage A, B and C colonic adenocarcinomas were analysed using semiquantitative immunohistochemistry and the results were related to patient outcome. Patients expressing nuclear beta-catenin in the primary tumour showed reduced survival compared to other patients (log rank p=0.028) and there was also an association with development of metastases follow-up (logistic regression p=0.024). Using multivariate analysis (Cox regression) co-expression of nuclear beta-catenin and c-Myc turned out to be the strongest marker of impaired prognosis (p=0.001, HR 5.26, 95% CI 1.93-14.36). Expression of non-membranous gamma-catenin, cyclin D1 and c-Myc alone failed to have independent prognostic significance in our study.

Adenocarcinoma↗

Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia.

Abnormal expression of cadherins and catenins plays a critical role in the initiation and progression of multiple human tumours. This study aimed to evaluate the immunoreactivity of E- and P-cadherin, beta- and gamma-catenin, and p120ctn in premalignant and malignant endometrial lesions and to correlate their membranous expression with clinicopathological features. In addition, we examined whether or not LOH and promoter hypermethylation of the CDH1 gene were associated with E-cadherin expression and clinicopathological variables. Finally, we studied the frequency of beta-catenin mutations in premalignant endometrial lesions. Immunohistochemical staining was performed in 21 atypical endometrial hyperplasias (AEHs), 95 endometrioid carcinomas (EECs), and 33 non-endometrioid carcinomas (NEECs). Reduced E-cadherin expression was observed in 57.8% of the cases, being more frequent in NEECs (87.1%, p = 0.001) and carcinomas of more advanced stage (85.7% of stage III-IV carcinomas, p = 0.01). LOH of CDH1 gene was found in 57.1% of NEECs but only in 22.5% of EECs (p = 0.011) and showed a trend towards association with reduced E-cadherin expression (p = 0.089). CDH1 promoter hypermethylation was found in 21.2% of endometrial carcinomas but was not associated with clinicopathological or immunohistochemical variables. Reduced expression of beta- and gamma-catenin and p120ctn was found in 76.1%, 94.3%, and 63.6% of the cases, respectively, being more frequent in lesions with reduced E-cadherin expression. In addition, beta-catenin, but not gamma-catenin or p120ctn expression, was associated with the histology of the lesion, since it was reduced in 35% of AEHs, 80.3% of EECs, and 96.9% of NEECs (p = 0.000). Mutations in exon 3 of the beta-catenin gene, associated with beta-catenin nuclear expression, were detected in 3 (14.0%) AEH, a frequency similar to that previously reported in this series of ECs. Finally, upregulation of P-cadherin was observed in 28.6% of cases. This alteration was associated with the histology of the lesion, since it was found in 9.5% of AEHs, 27.7% of EECs, and 46.2% of NEECs (p = 0.021).

Cadherins↗

Reduced expression of alpha-catenin, beta-catenin, and gamma-catenin is associated with high cell proliferative activity and poor differentiation in non-small cell lung cancer.

AIMS: To investigate the expression of catenins (alpha, beta, and gamma) in non-small cell lung carcinoma (NSCLC) and its relation to clinicopathological factors and prognosis. METHODS: The expression of catenins was analysed immunohistochemically in 261 patients with resected NSCLC, diagnosed between 1978 and 1996 in eastern Finland: The cell proliferation index of the tumours was analysed by means of an image analyser. The staining results were compared with clinicopathological characteristics and survival. RESULTS: Normal catenin staining was found significantly more often in adenocarcinomas than in squamous cell carcinomas or anaplastic/large cell carcinomas. Reduced staining of alpha-catenin, beta-catenin, and gamma-catenin was related to poor differentiation of the tumour. The tumours with reduced staining of beta-catenin or gamma-catenin often had higher cell proliferation activity. Nuclear staining of beta-catenin and gamma-catenin was found in 16 (7%) and 29 (13%) cases, respectively. This nuclear staining correlated directly with increased cell proliferation and inversely with membranous staining. In survival analyses the predictors of overall and disease free survival were stage and tumour type. The expression of catenins did not affect survival. CONCLUSIONS: The expression of alpha-catenin, beta-catenin, and gamma-catenin is related to histological type and differentiation in NSCLC, although catenins have no independent prognostic value. However, this study supports the important role of the nuclear accumulation of beta-catenin and gamma-catenin in highly proliferative cells.

Aged↗

Expression of E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin in bronchioloalveolar carcinoma and conventional pulmonary adenocarcinoma: an immunohistochemical study.

Bronchioloalveolar carcinoma (BAC) has features distinct from those of conventional pulmonary adenocarcinoma (CPA) in terms of its characteristic growth pattern along alveolar walls and intrapulmonary metastasis via the aerogenous route. We speculated, therefore, that BAC might differ from CPA in its capacity for cell-to-cell or cell-to-basement membrane adhesion. E-cadherin (E-CD), one of the most important elements of epithelial integrity molecules, is related to tumor metastasis in various organs. Differences of E-CD and associated catenin expressions between BAC and CPA, however, have not been elucidated. We examined the expression of E-CD and alpha-, beta- and gamma-catenin immunohistochemically in 18 BACs (9 mucinous, 7 nonmucinous, and 2 sclerosing) in comparison with CPAs, all of which were well-differentiated adenocarcinomas. In addition, we analyzed the correlation between the expression of these cell adhesion molecules and the presence of intrapulmonary metastasis, histologic subtypes, and cell proliferation activity. Clinicopathologically, we observed intrapulmonary metastases in 4 of the 18 BACs and none of the CPAs. In 14 of the 18 BACs, more than one-half of the tumor cells expressed E-CD, and the E-CD expression level was significantly higher in the BACs than in the CPAs. In addition, all of the BACs exhibited preserved membranous staining for E-CD, whereas in 5 of the 14 CPAs, the expression pattern was disorganized cytoplasmic staining; the difference was statistically significant. The Ki-67 labeling index was significantly lower in the BACs than in the CPAs. There were no appreciable differences in E-CD expression among the BAC subtypes. E-CD expression was significantly lower in the BACs with intrapulmonary metastasis than in the BACs without intrapulmonary metastasis. These findings indicated to us that BAC was distinct from CPA in terms of proliferation activity and expression of certain adhesion molecules and that E-CD downregulation was associated with a tendency toward intrapulmonary metastasis.

Adenocarcinoma↗

Expression of E-cadherin and alpha-, beta-, gamma-catenins in patients with bladder cancer: identification of gamma-catenin as a new prognostic marker of neoplastic progression in T1 superficial urothelial tumors.

Loss of intercellular adhesion facilitates tumor invasion. To clarify the relation between altered expression of cell adhesion molecules and progression of T1 superficial bladder tumors, 101 cases (71 T1 tumors, 30 T2/T3 tumors) were examined immunohistochemically for E-cadherin and alpha-, beta-, and gamma-catenins. A highly significant correlation was observed between the decreased expression of all molecules and increased TNM stage (P < .001). Univariate analysis, performed in cases of T1 tumors, revealed association of abnormal E-cadherin with beta-catenin diminution. Survival curves were established with the Kaplan-Meier method and analyzed according to clinical and histopathologic parameters using the log-rank test. Cox multivariate analysis revealed only gamma-catenin as an independent predictor of progression-free survival in patients with stage T1 bladder urothelial tumors. The characterization of T1 tumors that will progress could lead to the identification of patients who might benefit from surgery to avoid vesical muscle invasion and, consequently, metastasis.

Aged↗

The reduced expression of e-cadherin, alpha-catenin and gamma-catenin but not beta-catenin in human lung cancer.

Cadherins are Ca2+-dependent cell-cell adhesion molecules, and are involved in the formation and maintenance of the histo-architecture. Using a combination of biochemical and immunohistochemical methods, we analyzed the expression of cadherin-catenin complexes in 37 non-small cell lung carcinomas. In 19 cases, decreased expression of E-cadherin protein was observed. In 12 of them, decreased expression of alpha-catenin protein was also observed. Thus, decreased expression of alpha-catenin was apparently preceded by decreased expression of E-cadherin. In no cases was decreased expression of beta-catenin observed. In the 12 cases in which mRNA expression was analyzed by Northern blot analysis, decreased expression of mRNAs for E-cadherin and alpha-catenin was observed in 11 and 9 cases, respectively. In cases with reduced E-cadherin and alpha-catenin expression, immunohistochemistry revealed two types of staining pattern for the proteins. In the first type, almost all the cells in a tumor were stained weakly (homogeneous pattern). In the second type, different percentages of cells were stained strongly, the rest being almost negative for the staining (heterogeneous pattern).

Aged↗

Re-expression of E-cadherin, alpha-catenin and beta-catenin, but not of gamma-catenin, in metastatic tissue from breast cancer patients [seecomments].

Tumour cell invasion and metastasis are the processes which kill most cancer patients. Tumour cells with the greatest invasive and metastatic capacity may be those with the highest number of genetic aberrations. The present study has analysed the expression of several tumour-related proteins in both primary tumours and metastatic lesions from 34 breast cancer patients. Protein expression of p53, bcl-2, p21, cyclin D1, E-cadherin, alpha-catenin, beta-catenin, and gamma-catenin was investigated by immunohistochemistry (IHC) using monoclonal antibodies. Metastatic tissue showed a different expression profile from the primary tumour in most patients. The most significant finding was the re-expression of E-cadherin, alpha-catenin, and beta-catenin, and increased down-regulation of gamma-catenin, in metastatic lesions. These results demonstrate that tumour cells, when released from the primary site and after regrowth elsewhere, are capable of re-expression of adhesion molecules. gamma-catenin may play a different role in metastatic lesions than in primary tumours, since it is selectively down-regulated in tumour tissue at the metastatic site.

Breast Neoplasms↗

Identification of the domain of alpha-catenin involved in its association with beta-catenin and plakoglobin (gamma-catenin).

alpha-Catenin is a 102-kDa protein exhibiting homology to vincuin, and it forms complexes with cadherins or the tumor-suppressor gene product adenomatous polyposis coli through binding to beta-catenin or plakoglobin (gamma-catenin). The incorporation of alpha-catenin into the cadherin-catenin complexes is a prerequisite for expression of the cell-adhesive activity of cadherins. Using an in vitro assay system involving bacterially expressed proteins, we localized a region in alpha-catenin required for molecular interaction with beta-catenin and plakoglobin. Analysis of various truncated alpha-catenin molecules revealed that amino-terminal residues 48-163 are able to bind to beta-catenin and plakoglobin. Consistent with the observation that beta-catenin and plakoglobin bind to the same region of alpha-catenin, beta-catenin competed with the binding of plakoglobin to alpha-catenin and vice versa. Under the conditions used, beta-catenin bound to alpha-catenin with higher affinity than did plakoglobin. Scatchard analysis indicated that the affinity of the interaction between alpha-catenin and beta-catenin or that between alpha-catenin and plakoglobin was moderately strong (Kd = 3. 8 x 10(-8) and 7.7 x 10(-8), respectively). When transfected into L cells expressing E-cadherin, the amino-terminal region of alpha-catenin (from residue 1 to 226) formed complexes with beta-catenin supporting the in vitro binding experiment results.

Binding Sites↗

[Relationship between the expression of E-cadherin-catenins and alpha-, beta-, gamma-catenin and the metastasis and prognosis of breast cancer].

OBJECTIVE: To investigate the relationship between E-cadherin, alpha-, beta-, gamma-catenin expression and clinicopathological features and prognosis of breast cancer. METHODS: The expression of E-cadherin and alpha-, beta-, gamma-catenin in 40 breast cancer specimens was studied by the immunohistochemical method. The relationship between E-cadherin, alpha-, beta-, gamma-catenin expression and clinicopathological characteristics or survival time was analyzed respectively. RESULTS: The abnormal expression of E-cadherin and alpha-, beta-catenin was significantly correlated with lymph nodes and distant metastasis (P < 0.01, P < 0.05). The expression of E-cadherin and beta-catenin was also strictly correlated with surival time of breast cancer patients (P < 0.01). However, when all the four proteins (E-cadherin, alpha-, beta-, gamma-catenin) were analyzed as one group, a significant association was found between the abnormal expression of two or more of these four proteins and the metastasis and prognosis of breast cancer (P < 0.05). CONCLUSION: Lower expression of E-cadherin and beta-catenin could be used as an important marker of metastasis and prognosis of breast cancer. Moreover, when all the four proteins (E-cadherin, alpha-, beta-, gamma-catenin) are considered together, the accuracy and sensitivity predicting metastasis and prognosis of breast cancer could be increased.

Adult↗