Beta-catenin mutations in cell lines established from human colorectal cancers.
beta-catenin has functions as both an adhesion and a signaling molecule. Disruption of these functions through mutations of the beta-catenin gene (CTNNB1) may be important in the development of colorectal tumors. We examined the entire coding sequence of beta-catenin by reverse transcriptase-PCR (RT...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1997
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| _version_ | 1797075001507053568 |
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| author | Ilyas, M Tomlinson, I Rowan, A Pignatelli, M Bodmer, W |
| author_facet | Ilyas, M Tomlinson, I Rowan, A Pignatelli, M Bodmer, W |
| author_sort | Ilyas, M |
| collection | OXFORD |
| description | beta-catenin has functions as both an adhesion and a signaling molecule. Disruption of these functions through mutations of the beta-catenin gene (CTNNB1) may be important in the development of colorectal tumors. We examined the entire coding sequence of beta-catenin by reverse transcriptase-PCR (RT-PCR) and direct sequencing of 23 human colorectal cancer cell lines from 21 patients. In two cell lines, there was apparent instability of the beta-catenin mRNA. Five different mutations (26%) were found in the remaining 21cell lines (from 19 patients). A three-base deletion (codon 45) was identified in the cell line HCT 116, whereas cell lines SW 48, HCA 46, CACO 2, and Colo 201 each contained single-base missense mutations (codons 33, 183, 245, and 287, respectively). All 23 cell lines had full-length beta-catenin protein that was detectable by Western blotting and that coprecipitated with E-cadherin. In three of the cell lines with CTNNB1 mutations, complexes of beta-catenin with alpha-catenin and APC were detectable. In SW48 and HCA 46, however, we did not detect complexes of beta-catenin protein with alpha-catenin and APC, respectively. These results show that selection of CTNNB1 mutations occurs in up to 26% of colorectal cancers from which cell lines are derived. In these cases, mutation selection is probably for altered beta-catenin function, which may significantly alter intracellular signaling and intercellular adhesion and may serve as a complement to APC mutations in the early stages of tumorigenesis. |
| first_indexed | 2024-03-06T23:44:15Z |
| format | Journal article |
| id | oxford-uuid:705ccafa-4947-4114-821f-7dc49a4fd909 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:44:15Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:705ccafa-4947-4114-821f-7dc49a4fd9092022-03-26T19:36:38ZBeta-catenin mutations in cell lines established from human colorectal cancers.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:705ccafa-4947-4114-821f-7dc49a4fd909EnglishSymplectic Elements at Oxford1997Ilyas, MTomlinson, IRowan, APignatelli, MBodmer, Wbeta-catenin has functions as both an adhesion and a signaling molecule. Disruption of these functions through mutations of the beta-catenin gene (CTNNB1) may be important in the development of colorectal tumors. We examined the entire coding sequence of beta-catenin by reverse transcriptase-PCR (RT-PCR) and direct sequencing of 23 human colorectal cancer cell lines from 21 patients. In two cell lines, there was apparent instability of the beta-catenin mRNA. Five different mutations (26%) were found in the remaining 21cell lines (from 19 patients). A three-base deletion (codon 45) was identified in the cell line HCT 116, whereas cell lines SW 48, HCA 46, CACO 2, and Colo 201 each contained single-base missense mutations (codons 33, 183, 245, and 287, respectively). All 23 cell lines had full-length beta-catenin protein that was detectable by Western blotting and that coprecipitated with E-cadherin. In three of the cell lines with CTNNB1 mutations, complexes of beta-catenin with alpha-catenin and APC were detectable. In SW48 and HCA 46, however, we did not detect complexes of beta-catenin protein with alpha-catenin and APC, respectively. These results show that selection of CTNNB1 mutations occurs in up to 26% of colorectal cancers from which cell lines are derived. In these cases, mutation selection is probably for altered beta-catenin function, which may significantly alter intracellular signaling and intercellular adhesion and may serve as a complement to APC mutations in the early stages of tumorigenesis. |
| spellingShingle | Ilyas, M Tomlinson, I Rowan, A Pignatelli, M Bodmer, W Beta-catenin mutations in cell lines established from human colorectal cancers. |
| title | Beta-catenin mutations in cell lines established from human colorectal cancers. |
| title_full | Beta-catenin mutations in cell lines established from human colorectal cancers. |
| title_fullStr | Beta-catenin mutations in cell lines established from human colorectal cancers. |
| title_full_unstemmed | Beta-catenin mutations in cell lines established from human colorectal cancers. |
| title_short | Beta-catenin mutations in cell lines established from human colorectal cancers. |
| title_sort | beta catenin mutations in cell lines established from human colorectal cancers |
| work_keys_str_mv | AT ilyasm betacateninmutationsincelllinesestablishedfromhumancolorectalcancers AT tomlinsoni betacateninmutationsincelllinesestablishedfromhumancolorectalcancers AT rowana betacateninmutationsincelllinesestablishedfromhumancolorectalcancers AT pignatellim betacateninmutationsincelllinesestablishedfromhumancolorectalcancers AT bodmerw betacateninmutationsincelllinesestablishedfromhumancolorectalcancers |