Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis.
beta-catenin is involved in E-cadherin-mediated cell adhesion, intracellular signal transduction, and also interacts with adenomatous polyposis coli (APC) protein. We previously found that 31% of colorectal adenomas and 84% of carcinomas showed reduced membranous staining of beta-catenin, while 46%...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2002
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| _version_ | 1797052115818905600 |
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| author | Hao, X Frayling, I Willcocks, T Han, W Tomlinson, I Pignatelli, M Pretlow, T Talbot, I |
| author_facet | Hao, X Frayling, I Willcocks, T Han, W Tomlinson, I Pignatelli, M Pretlow, T Talbot, I |
| author_sort | Hao, X |
| collection | OXFORD |
| description | beta-catenin is involved in E-cadherin-mediated cell adhesion, intracellular signal transduction, and also interacts with adenomatous polyposis coli (APC) protein. We previously found that 31% of colorectal adenomas and 84% of carcinomas showed reduced membranous staining of beta-catenin, while 46% of adenomas and 79% of carcinomas displayed beta-catenin nuclear expression. Importantly, a reciprocal relationship between reduced membranous and increased nuclear beta-catenin expression was demonstrated in the development from adenoma to carcinoma. To clarify whether this relates to an abnormality of the APC gene ( APC), we have now studied allele loss in microdissected tissues from 74 adenomas and 21 carcinomas (sporadic cases, previously immunostained for beta-catenin) by analysis of the microsatellites D5S346, D5S82 and D5S299. Fifty-five tumors (57.8%) showed allele loss at APC (no difference between adenomas and carcinomas). Thirty-one of these 55 (31/55, 56.4%) displayed both increased nuclear localization and reduced membranous staining of beta-catenin, and thirteen tumors (13/55, 23.6%) manifested either nuclear expression without changes in membranous expression or reduced membranous staining without nuclear expression (9 and 4 cases, respectively), while 11 (11/55, 20.0%) preserved normal membranous expression. Adenomas and carcinomas showing both nuclear and reduced membranous expression of beta-catenin, compared with those with normal membranous expression, tended to show allele loss ( P<0.01). In addition, 24 (24/95, 25.6%) tumors showed a change in the pattern of beta-catenin expression, but did not exhibit allele loss. These results suggest that although there may be a number of mechanisms responsible for changes in beta-catenin expression in colorectal tumors, dysfunction of APC may be the major cause of this phenomenon. |
| first_indexed | 2024-03-06T18:28:12Z |
| format | Journal article |
| id | oxford-uuid:08b8a47e-1f87-4b49-b83d-d58de8f94771 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:28:12Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:08b8a47e-1f87-4b49-b83d-d58de8f947712022-03-26T09:14:22ZBeta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:08b8a47e-1f87-4b49-b83d-d58de8f94771EnglishSymplectic Elements at Oxford2002Hao, XFrayling, IWillcocks, THan, WTomlinson, IPignatelli, MPretlow, TTalbot, Ibeta-catenin is involved in E-cadherin-mediated cell adhesion, intracellular signal transduction, and also interacts with adenomatous polyposis coli (APC) protein. We previously found that 31% of colorectal adenomas and 84% of carcinomas showed reduced membranous staining of beta-catenin, while 46% of adenomas and 79% of carcinomas displayed beta-catenin nuclear expression. Importantly, a reciprocal relationship between reduced membranous and increased nuclear beta-catenin expression was demonstrated in the development from adenoma to carcinoma. To clarify whether this relates to an abnormality of the APC gene ( APC), we have now studied allele loss in microdissected tissues from 74 adenomas and 21 carcinomas (sporadic cases, previously immunostained for beta-catenin) by analysis of the microsatellites D5S346, D5S82 and D5S299. Fifty-five tumors (57.8%) showed allele loss at APC (no difference between adenomas and carcinomas). Thirty-one of these 55 (31/55, 56.4%) displayed both increased nuclear localization and reduced membranous staining of beta-catenin, and thirteen tumors (13/55, 23.6%) manifested either nuclear expression without changes in membranous expression or reduced membranous staining without nuclear expression (9 and 4 cases, respectively), while 11 (11/55, 20.0%) preserved normal membranous expression. Adenomas and carcinomas showing both nuclear and reduced membranous expression of beta-catenin, compared with those with normal membranous expression, tended to show allele loss ( P<0.01). In addition, 24 (24/95, 25.6%) tumors showed a change in the pattern of beta-catenin expression, but did not exhibit allele loss. These results suggest that although there may be a number of mechanisms responsible for changes in beta-catenin expression in colorectal tumors, dysfunction of APC may be the major cause of this phenomenon. |
| spellingShingle | Hao, X Frayling, I Willcocks, T Han, W Tomlinson, I Pignatelli, M Pretlow, T Talbot, I Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. |
| title | Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. |
| title_full | Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. |
| title_fullStr | Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. |
| title_full_unstemmed | Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. |
| title_short | Beta-catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis. |
| title_sort | beta catenin expression and allelic loss at apc in sporadic colorectal carcinogenesis |
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