Possible association between higher beta-catenin mRNA expression and mutated beta-catenin in sporadic desmoid tumors: real-time semiquantitative assay by TaqMan polymerase chain reaction.
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| Abstract |
We screened for genetic alterations of adenomatous polyposis coli (APC) and beta-catenin genes in 17 frozen specimens from 12 cases of sporadic desmoid tumors and then subdivided these cases into two groups according to the results of mutational analysis. We further examined mRNA expression of beta-catenin and cyclin D1 by TaqMan PCR and compared the mRNA expression within both groups. Single-strand conformation polymorphism analysis followed by DNA direct sequencing revealed beta-catenin mutation in 3 of 12 cases (6 of 17 specimens), whereas no APC missense mutations in the mutation cluster region were found. TaqMan PCR revealed extremely higher mRNA expression of beta-catenin and cyclin D1 in desmoid tumors, compared with those of normal skeletal muscles. In the beta-catenin mutated group, cyclin D1 mRNA expression was significantly higher than that of the beta-catenin wild-type group (p = 0.0120, Mann-Whitney U test). In addition, in the beta-catenin mutated group, beta-catenin mRNA expression was also significantly higher than that of the beta-catenin wild-type group (p = 0.0036, Mann-Whitney U test). All cases of desmoid tumors showed detectable beta-catenin nuclear expression immunohistochemically. These results suggest that a continuously elevated beta-catenin protein level caused by the beta-catenin mutation itself may have a stronger power that can transactivate transcription in vivo. Furthermore, the results provide a possible association between higher beta-catenin mRNA expression and mutated beta-catenin in sporadic desmoid tumors. This may suggest that the beta-catenin gene may be up-regulated by mutated or continuously elevated beta-catenin protein, that is, the beta-catenin gene may also be one of the targeted genes in the APC-beta-catenin-Tcf pathway.
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| Authors | Tsuyoshi Saito, Yoshinao Oda, Ken-ichi Kawaguchi, Kazuhiro Tanaka, Shuichi Matsuda, Sadafumi Tamiya, Yukihide Iwamoto, Masazumi Tsuneyoshi |
| Journal | Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 82 Issue 1 Pg. 97-103 (Jan 2002) ISSN: 0023-6837 [Print] United States |
| PMID | 11796830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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