Aurora-A gene is frequently amplified in basal-like breast cancer.
Aurora-A is a serine-threonine kinase having vital cellular functions in mitosis and is a promising target for therapy in treating patients with cancer. This study assesses the clinicopathological associations of AURKA gene amplification in clinical breast tumors and association of gene copy number with its mRNA and protein expression in breast cancer cell lines. In this pilot study, we examined Aurora-A gene (AURKA) amplification in 126 clinical breast tumors by chromogenic in situ hybridisation (CISH). AURKA amplification (found in 21%) showed an association with basal-like tumor phenotype (p=0.046). A separate series of basal-like breast tumors (n=26) provided further evidence of the importance of AURKA in these tumors. AURKA amplification status was associated with immunohistochemically detectable Aurora-A protein expression (p<0.0001). In breast cancer cell lines, gene amplification was strongly associated with high mRNA expression (p<0.0001). JIMT-1 cell line was found as a possible in vitro model system for testing Aurora-A inhibitors, since it has been classified as basal-like breast cancer and here it showed both AURKA gene amplification and elevated mRNA expression. AURKA gene amplification is a common genetic aberration in breast cancer, especially in tumors displaying basal-like phenotype. Thus, these patients might be suitable candidates for future targeted therapies with Aurora-A inhibitors.
Staff
Synnöve
S
Institute of Medical Technology, University and University Hospital of Tampere, Tampere, Finland. synnove.staff@uta.fi
Isola
Jorma
J
Jumppanen
Mervi
M
Tanner
Minna
M
D064096:Aurora Kinase A; D064127:Aurora Kinases; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005784:Gene Amplification; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D018295:Neoplasms, Basal Cell / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases