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Increased nucleotide polymorphic changes in the 5′-untranslated region of δ-catenin (CTNND2) gene in prostate cancer

Oncogene volume 28, pages 555–564 (2009)Cite this article

Abstract

Cancer pathogenesis involves multiple genetic and epigenetic alterations, which result in oncogenic changes in gene expression. δ-Catenin (CTNND2) is overexpressed in cancer, although the mechanisms of its upregulation are highly variable. Here we report that in prostate cancer, the methylation of CpG islands in the δ-catenin promoter was not a primary regulatory event. There was also no δ-catenin gene amplification. However, using the single-strand conformation polymorphism analysis, we observed the increased nucleotide changes in the 5′-untranslated region of δ-catenin gene in human prostate cancer. At least one such change (−9 G>A) is a true somatic point mutation associated with a high Gleason's score, poorly differentiated prostatic adenocarcinoma. Laser capture microdissection coupled with PCR analyses detected the mutation only in cancerous but not in the adjacent benign prostatic tissues. Using chimeric genes encoding the luciferase reporter, we found that this mutation, but not a random mutation or a mutation that disrupts an upstream open reading frame, resulted in a remarkably higher expression and enzyme activity. This mutation did not affect transcriptional efficiency, suggesting that it promotes δ-catenin translation. This is the first report of δ-catenin gene mutation in cancer and supports the notion that multiple mechanisms contribute to its increased expression in carcinogenesis.

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Acknowledgements

We thank Melissa Clark and GW Lanford for excellent technical assistance, and Lu laboratory members for many helpful discussions. This study was supported in part by NIH/NCI (CA111891) and the Department of Defense (PC040569) grants (QL).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC, USA

    T Wang, Y-H Chen, Y Zeng, J Zhang, J-P Lu, B Jeansonne & Q Lu

  2. Department of Pathology and Laboratory Medicine, Brody School of Medicine, East Carolina University, Greenville, NC, USA

    H Hong

  3. Leo Jenkins Cancer Center, Brody School of Medicine, East Carolina University, Greenville, NC, USA

    Q Lu

  4. Department of Oncology, Capital Medical University, Beijing, China

    T Wang

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  1. T Wang
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Correspondence to Q Lu.

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Supplementary information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Wang, T., Chen, YH., Hong, H. et al. Increased nucleotide polymorphic changes in the 5′-untranslated region of δ-catenin (CTNND2) gene in prostate cancer. Oncogene 28, 555–564 (2009). https://doi.org/10.1038/onc.2008.399

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