Functional analysis of the aurora kinase A Ile31 allelic variant in the human prostate

Noa Matarasso, Anat Bar-Shira, Uri Rozovsky, Serena Rosner and Avi Orr-Urtreger

Year 2007, Volume 9, Issue 9

Abstract

Overexpression of the centrosome-associated serine/threonine kinase Aurora Kinase A (AURKA) has been demonstrated in both advanced prostate cancer and in high-grade prostatic intraepithelial neoplasia lesions. The single nucleotide polymorphism, T91A (Phe31Ile), has been implicated in AURKA overexpression and was suggested as a low-penetrance susceptibility allele in multiple human cancers, including prostate cancer. We studied the transcriptional consequences of the AURKA Ile31 allele in 28 commercial normal prostate tissue RNA samples (median age 27 years). Significant overexpression of AURKA was demonstrated in homozygous and heterozygous AURKA Ile31 prostate RNAs (2.07-fold and 1.93-fold, respectively, p<0.05). Expression levels of 1,509 genes differentiated between samples homozygous for Phe31 and Ile31 alleles (p=0.05). Gene Ontology classification revealed over-representation of cell cycle arrest, ubiquitin cycle, anti-apoptosis and angiogenesis related genes. When these hypothesis generating results were subjected to more stringent statistical criteria, overexpression of a novel transcript of the NKTR (Natural Killer Tumor Recognition) gene was revealed and validated in the homozygous Ile31 samples (2.6-fold, p<0.05). In summary, our data suggest an association between the AURKA Ile31 allele and an altered transcriptome in normal non-neoplastic prostates.

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