The INTERACTIONS OF APC, E‐CADHERIN AND Β‐CATENIN IN TUMOUR DEVELOPMENT AND PROGRESSION

Ilyas, Mohammed Iyoob Mohammed; Tomlinson, I.

doi:10.1002/(sici)1096-9896(199706)182:2<128::aid-path839>3.3.co;2-h

Cited by 18 publications

(21 citation statements)

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“…The net result of APC mutation is an increase in cytoplasmic catenin, which may then trigger a cascade of events resulting in the initiation of adenomas. 25 However, the exact mechanisms behind the cytoplasmic expression of catenins remain to be clarified in future studies.…”

Section: Discussionmentioning

confidence: 99%

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Ropponen

Eskelinen

Lipponen

et al. 1999

Journal of Clinical Pathology

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Aims-To investigate catenin expression in surgically resected human colorectal cancers to evaluate its prognostic value during long term follow up. Methods-Immunohistochemistry was used to compare the expression of catenin with conventional prognostic factors in 187 colorectal cancer patients treated in Kuopio University Hospital and followed up for a mean of 14 years. The hypothesis that the intensity of expression of catenin and its distribution in cancer cells is correlated with survival was tested with the log-rank test, hazard ratios, and their confidence intervals. Results-Uniform membranous catenin staining localised to the intercellular borders was observed in 46% of the tumours; 55% of all tumours had either heterogeneous or negative catenin expression, and staining intensity was either negative or weak in 42% of the tumours. The cancer related and recurrence-free survival rates were lower among patients with a weak catenin intensity in tumour epithelium (p < 0.001), a low fraction of positive tumour cells (p < 0.001), and an additional cytoplasmic accumulation of catenin (p < 0.001). In multivariate analysis, the intensity of catenin expression in tumour epithelium predicted cancer related survival independently; catenin localisation in tumour epithelium was an independent prognostic factor of recurrence-free survival in the group as a whole and in the T1-3N0M0 tumour subgroup. Conclusions-A low proportion of positive carcinoma cells, additional cytoplasmic accumulation of catenin, and reduced expression intensity in tumour epithelium predict a poor survival rate. The results suggest that catenin has prognostic significance in colorectal cancer. (J Clin Pathol 1999;52:10-16)

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Section: Discussionmentioning

confidence: 99%

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Ropponen

Eskelinen

Lipponen

et al. 1999

Journal of Clinical Pathology

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“…The tumour suppressor APC gene plays an important role in colon tumour initiation, as shown previously18; that is, APC is thought to mediate the interaction between β-catenin and glycogen synthase kinase 3β (GSK-3β). GSK-3β phosphorylates β-catenin which targets β-catenin for ubiquitin dependent, proteosome mediated degradation 19…”

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confidence: 81%

Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane

Kishimoto

Takata

Jinnai

et al. 2000

Gut

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Background-Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to protect against the development of colon cancer. However, the mechanism(s) by which NSAIDs exert their eVects is not clear. Aims-The aim of this study was to examine the eVects of NSAIDs on mRNA expression of tumour suppressor adenomatous polyposis coli (APC) gene in rat colon mucosa. Methods-Starting at six weeks of age, three groups of rats (groups 1, 2, and 3) were treated with azoxymethane (AOM), a colon specific carcinogen, and another three groups (groups 4, 5, and 6) were not given AOM. Groups 2 and 3 were given 10 mg/kg of sulindac or etodolac, respectively, three times weekly during the experiment. Groups 4 and 5 were also given sulindac or etodolac, respectively, in the same manner as in groups 2 and 3. Group 6 (untreated control) was not given any agent (AOM or NSAIDs). At 10 weeks of age, preneoplastic lesions (aberrant crypt foci (ACF)) induced by AOM in the colon were counted, and the level of expression of APC mRNA in the colonic mucosa was estimated by the reverse transcription-competitive polymerase chain reaction method and northern blot analysis. Results-Mean occurrence of ACF in rats in groups 2 and 3 was reduced to approximately 50% of that in group 1. The level of APC mRNA expression in group 1 (AOM alone) was lower than that in group 6 (untreated control) (p<0.05); however, levels of APC mRNA expression in groups 2, 3, 4, and 5, to which NSAIDs had been administered, were significantly increased compared with levels in groups 1 and 6 (p<0.01). Conclusions-Both sulindac and etodolac reduced the occurrence of ACF and induced an increase in APC mRNA in rat colon mucosa.

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“…2 Many studies have suggested that the E-cadherin adhesion system is disturbed in cancer cells and observations in experimental and human carcinomas have shown that reduced expression of E-cadherin induces dedifferentiation and invasiveness in tumour cells. [2][3][4] Catenins, the -subunit, -subunit, and -subunit/ plakoglobin, are a group of proteins that interact with the intercellular domain of E-cadherin, resulting in complexes of E-cadherin/ -catenin/ -catenin or E-cadherin/ -catenin/ -catenin. 5 -Catenin shows sequence similarity to vinculin and interacts with the cytoskeletal proteins.…”

Section: Introductionmentioning

confidence: 99%

Immunolocalization of the fodrin, E-cadherin, and ?-catenin adhesion complex in infiltrating ductal carcinoma of the breast?comparison with anin vitro model

et al. 1999

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Fodrin, E‐cadherin, and β‐catenin immunolocalization was studied in 54 cases of infiltrating ductal carcinoma of the breast and compared with an in vitro model in order to study the dynamic relationship between these components of an adhesion complex. In low‐grade tumours, the staining patterns were similar for both fodrin and E‐cadherin, with localization of these proteins to the cell membranes. β‐Catenin showed reduced membrane staining compared with non‐neoplastic epithelium. High‐grade tumours displayed strong membranous as well as cytoplasmic immunolocalization of fodrin, while E‐cadherin staining was fragmented or lost from the membranes, with only occasional weak intracellular staining. β‐Catenin showed fragmented membrane staining and cytoplasmic accumulation. In addition, nuclear staining of β‐catenin was occasionally observed. In a v‐src‐transformed MDCK cell line, following 15min of src activation, β‐catenin began to detach from the cell membrane and localize to the cytoplasm, while fodrin and E‐cadherin remained unchanged. After 30–45min of src activation, the cells lost their cuboidal shape and began to lose cell‐to‐cell contact. Fodrin staining remained mostly membranous while that of E‐cadherin and β‐catenin was fragmented and spiky. After 60min of src activation, fodrin localized completely in the cell cytoplasm, while E‐cadherin and β‐catenin were partly cytoplasmic with fragmented and spiky membranous staining. Occasionally, β‐catenin was seen in the nucleus. Both in vivo and in vitro findings clearly demonstrated a disruption of the E‐cadherin/β‐catenin/fodrin/cytoskeleton linkage concomitant with the loss of cell‐to‐cell adhesion and change in cell shape, from epithelioid to a fibroblastoid phenotype. Membranous localization of E‐cadherin showed a positive correlation with oestrogen and progesterone expression, whereas loss of membranous E‐cadherin and cytoplasmic accumulation of fodrin was more often observed in high‐grade carcinomas and showed a positive correlation with p53 expression. Copyright © 1999 John Wiley & Sons, Ltd.

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The INTERACTIONS OF APC, E‐CADHERIN AND Β‐CATENIN IN TUMOUR DEVELOPMENT AND PROGRESSION

Cited by 18 publications

References 0 publications

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Reduced expression of alpha catenin is associated with poor prognosis in colorectal carcinoma

Sulindac and a cyclooxygenase-2 inhibitor, etodolac, increase APC mRNA in the colon of rats treated with azoxymethane

Immunolocalization of the fodrin, E-cadherin, and ?-catenin adhesion complex in infiltrating ductal carcinoma of the breast?comparison with anin vitro model

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