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Aberrant nuclear localization of beta-catenin without genetic alterations in beta-catenin or Axin genes in esophageal cancer.
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Samples were obtained from 50 esophageal cancer patients.Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients.Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa.
Affiliation: Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. dr_kudo@yahoo.co.jp
ABSTRACT
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Background: beta-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. beta-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of beta-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the beta-catenin gene and Axin gene in esophageal squamous cell carcinoma. Materials and methods: Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for beta-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the beta-catenin gene and Axin gene were performed on tumors with nuclear beta-catenin expression. Results: Four (8%) esophageal cancer tissues showed high nuclear beta-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear beta-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of beta-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in beta-catenin exon 3 in the four cases with nuclear beta-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa. Conclusion: A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of beta-catenin accompanied with increased cyclin D1 expression. Mutations in beta-catenin or axin genes are not responsible for this abnormal localization of beta-catenin. Related in: MedlinePlus |
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Figure 3: Genetic alterations of the Axin gene in esophageal squamous cell carcinoma. Splicing variant is indicated by two-headed arrows. Mentions: We then searched for mutational changes in the Axin gene. Axin gene mutation may have caused the abnormal distribution of β-catenin. We examined the Axin cDNA in four cases showing nuclear localization of β-catenin protein. Sequencing analysis of the Axin cDNA revealed a splicing variant (108 bp deletion, position 2302–2409) and a normal cDNA in two of the cases tested. We sequenced the cDNA from the normal mucosa in these cases, and the same variant was found. This deletion affected the whole exon 9 (Fig. 3). Thus neither β-catenin exon 3 nor Axin gene mutation was responsible for the aberrant localization of β-catenin in the 4 cases. |
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Affiliation: Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. dr_kudo@yahoo.co.jp
Background: beta-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. beta-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of beta-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the beta-catenin gene and Axin gene in esophageal squamous cell carcinoma.
Materials and methods: Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for beta-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the beta-catenin gene and Axin gene were performed on tumors with nuclear beta-catenin expression.
Results: Four (8%) esophageal cancer tissues showed high nuclear beta-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear beta-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of beta-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in beta-catenin exon 3 in the four cases with nuclear beta-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa.
Conclusion: A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of beta-catenin accompanied with increased cyclin D1 expression. Mutations in beta-catenin or axin genes are not responsible for this abnormal localization of beta-catenin.
