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

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Yan-Hua Chen (Creator)

Heng Hong (Creator)

Beverly Jeansonne (Creator)

Qun Lu (Creator)

Jian-Ping Lu (Creator)

Tao Wang (Creator)

Yan Zeng (Creator)

Jiao Zhang (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Cancer pathogenesis involves multiple genetic and epigenetic alterations, which result in oncogenic changes in gene expression. d-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 d-catenin promoter was not a primary regulatory event. There was also no d-catenin gene amplification. However, using Single-Strand onformation Polymorphism analysis, we observed the increased nucleotide changes in the 5'-untranslated region of d-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\r\nmicrodissection 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\r\ntranscriptional efficiency, suggesting that it promotes d-catenin translation. This is the first report of d-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

Additional Information

Publication

Other

Oncogene\; 28:4 p. 555-564

Language: English

Date: 2023

Subjects

Single-strand conformation polymorphism;Single nucleotide polymorphism;5'UTR mutation;Methylation;Gene amplification

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