Overexpression of aurora B kinase (AURKB) in primary non-small cell lung carcinoma is frequent, generally driven from one allele, and correlates with the level of genetic instability

Aurora kinases are key regulators of chromosome segregation during mitosis. We have previously shown by microarray analysis of primary lung carcinomas and matched normal tissue that AURKB (22 out of 37) and AURKA (15 out of 37) transcripts are frequently over-represented in these tumours. We now con...

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Vydáno v:	British journal of cancer Ročník 93; číslo 6; s. 719 - 729
Hlavní autoři:	Smith, S L, Bowers, N L, Betticher, D C, Gautschi, O, Ratschiller, D, Hoban, P R, Booton, R, Santibáñez-Koref, M F, Heighway, J
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 19.09.2005 Nature Publishing Group
Témata:	Allelic Imbalance Antigens, Neoplasm - genetics Antigens, Neoplasm - metabolism Aurora Kinase A Aurora Kinase B Aurora Kinases Biological and medical sciences Biomarkers, Tumor - metabolism Biomedical and Life Sciences Biomedicine Blotting, Western Cancer Research Carcinoma, Non-Small-Cell Lung - enzymology Carcinoma, Non-Small-Cell Lung - pathology Catalytic Domain DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Drug Resistance Epidemiology Epithelial Cells - metabolism Epithelial Cells - pathology Gene expression Gene Expression Regulation, Enzymologic Genes, Tumor Suppressor Genetics and Genomics Genomics Humans Kinases Lung cancer Lung Neoplasms - enzymology Lung Neoplasms - pathology Medical research Medical sciences Microsatellite Repeats Molecular Medicine Oncology Pneumology Polymorphism, Restriction Fragment Length Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Reverse Transcriptase Polymerase Chain Reaction Serine Proteinase Inhibitors - genetics Serine Proteinase Inhibitors - metabolism Serpins - genetics Serpins - metabolism Telomerase - genetics Telomerase - metabolism Tumors Tumors of the respiratory system and mediastinum Up-Regulation United Kingdom > UK lung cancer genetic instability stem cells aurora Lung disease Respiratory disease Lung cancer Stem cell Gene overexpression Malignant tumor non-small cell lung carcinoma Genetic instability Allele Cancerology Aurora B kinase Primary Bronchus disease Frequency Genetics
ISSN:	0007-0920, 1532-1827
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Shrnutí:	Aurora kinases are key regulators of chromosome segregation during mitosis. We have previously shown by microarray analysis of primary lung carcinomas and matched normal tissue that AURKB (22 out of 37) and AURKA (15 out of 37) transcripts are frequently over-represented in these tumours. We now confirm these observations in a second series of 44 carcinomas and also show that aurora B kinase protein levels are raised in the tumours compared to normal tissue. Elevated levels of expression in tumours are not a consequence of high-level amplification of the AURKB gene. Using a coding sequence polymorphism we show that in most cases (seven out of nine) tumour expression is predominantly driven from one AURKB allele. Given the function of aurora B kinase, we examined whether there was an association between expression levels and genetic instability. We defined two groups of high and low AURKB expression. Using a panel of 10 microsatellite markers, we found that the group showing the higher level of expression had a higher frequency of allelic imbalance ( P =0.0012). Analysis of a number of other genes that are strongly and specifically expressed in tumour over normal lung, including SERPINB5, TERT and PRAME, showed marked allelic expression imbalances in the tumour tissue in the context of balanced or only marginally imbalanced relative allelic copy numbers. Our data support a model of early carcinogenesis wherein defects in the process of inactivation of lung stem-cell associated genes during differentiation, contributes to the development of carcinogenesis.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work
ISSN:	0007-0920 1532-1827
DOI:	10.1038/sj.bjc.6602779