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β‐Catenin ( CTNNB1 ) gene amplification: A new mechanism of protein overexpression in cancer
Author(s) -
Suriano Gianpaolo,
Vrcelj Nikoleta,
Senz Janine,
Ferreira Paulo,
Masoudi Hamid,
Cox Kelley,
Nabais Sergio,
Lopes Carlos,
Machado José Carlos,
Seruca Raquel,
Carneiro Fatima,
Huntsman David G.
Publication year - 2005
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.20135
Subject(s) - cyclin d1 , carcinogenesis , microbiology and biotechnology , chromosomal translocation , cancer , biology , catenin , cancer research , gene silencing , cancer cell , gene , genetics , wnt signaling pathway , cell cycle
Abstract β‐Catenin nuclear translocation is frequently observed in different types of malignancies, including gastric cancer. In gastric cancer, however, the molecular mechanisms leading to accumulation of this protein in the nucleus remain unknown. In this setting, β‐catenin ( CTNNB1 ) mutations have been reported, but studies of mutation frequency have yielded conflicting results. Mutations or silencing of other partners of β‐catenin (i.e., APC and AXIN ) are also considered rare genetic events in gastric tumorigenesis. Gene amplification is a common mechanism of activation and/or overexpression of oncogenes in gastric and other cancers. In this study, we investigated whether gene amplification is a possible mechanism of β‐catenin activation in gastric cancer by determining its presence in 49 patients with gastric cancer and two gastric‐derived cell lines (KATO III and ST2957). Using fluorescence in situ hybridization, we identified β‐catenin amplification in one of the tumor samples as well as in KATO III cells. β‐Catenin immunostaining revealed nuclear translocation of the protein in both cases. In the KATO III cells, β‐catenin overexpression was confirmed by quantitative real‐time PCR and Western blot analyses and β‐catenin gene amplification by Southern blot analysis and multiplex ligation probe amplification. In the KATO III cell line, no correlation was found between β‐catenin nuclear translocation and increased expression of the WNT1 target gene CCND1 (cyclin D1). Our data suggest that gene amplification is a possible mechanism of β‐catenin overexpression in cancer. © 2004 Wiley‐Liss, Inc.