Increased nucleotide polymorphic changes in the 5'-untranslated region of δ-catenin (CTNND2) gene in prostate cancer
Wang, Tao; Chen, Yan-Hua; Hong, Heng; Zeng, Yan; Zhang, Jiao; Lu, Jian-Ping; Jeansonne, Beverly; Lu, Qun
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 δ-catenin promoter was not a primary regulatory event. There was also no δ-catenin gene amplification. However, using Single-Strand onformation 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 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. Originally published ncogene, Vol. 28, No. 4, Jan 2009
Wang, Tao, & Chen, Yan-Hua, & Hong, Heng, & Zeng, Yan, & Zhang, Jiao, & Lu, Jian-Ping, & Jeansonne, Beverly, & Lu, Qun. (January 2009). Increased nucleotide polymorphic changes in the 5'-untranslated region of δ-catenin (CTNND2) gene in prostate cancer. Oncogene, 28(4), 555- 564. Retrieved from http://hdl.handle.net/10342/3434
Wang, Tao, and Chen, Yan-Hua, and Hong, Heng, and Zeng, Yan, and Zhang, Jiao, and Lu, Jian-Ping, and Jeansonne, Beverly, and Lu, Qun. "Increased nucleotide polymorphic changes in the 5'-untranslated region of δ-catenin (CTNND2) gene in prostate cancer". Oncogene. 28:4. (555-564), January 2009. December 16, 2018. http://hdl.handle.net/10342/3434.
Wang, Tao and Chen, Yan-Hua and Hong, Heng and Zeng, Yan and Zhang, Jiao and Lu, Jian-Ping and Jeansonne, Beverly and Lu, Qun, "Increased nucleotide polymorphic changes in the 5'-untranslated region of δ-catenin (CTNND2) gene in prostate cancer," Oncogene 28, no. 4 (January 2009), http://hdl.handle.net/10342/3434 (accessed December 16, 2018).
Wang, Tao, Chen, Yan-Hua, Hong, Heng, Zeng, Yan, Zhang, Jiao, Lu, Jian-Ping, Jeansonne, Beverly, Lu, Qun. Increased nucleotide polymorphic changes in the 5'-untranslated region of δ-catenin (CTNND2) gene in prostate cancer. Oncogene. January 2009; 28(4): 555-564. http://hdl.handle.net/10342/3434. Accessed December 16, 2018.
East Carolina University