Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients.
The serine/threonine protein kinase aurora B, a key regulator of mitosis, is emerging as a novel drug target for cancer treatment. Aurora B overexpression has been previously documented by immunohistochemistry in several types of human tumors. We assessed aurora B expression in a series of 160 non-small cell lung cancer (NSCLC) samples (60% stage I, 21% stage II, 11% stage III, and 8% stage IV). In addition, we determined the expression of survivin and p16, two molecules also involved in cell cycle control. Aurora B was expressed selectively in tumor cells compared with normal epithelium. Aurora B expression was significantly correlated with expression of survivin in the nucleus (P < 0.0001), but not with expression of p16 (P = 0.134). High aurora B expression levels were significantly associated with older age (P = 0.012), male sex (P = 0.013), squamous cell carcinoma histology (P = 0.001), poor tumor differentiation grade (P = 0.007), and lymph node invasion (P = 0.037), in the subset of radically resected patients in our series. In addition, aurora B expression predicted shorter survival for the patients with adenocarcinoma histology, at both univariate (P = 0.020) and multivariate (P = 0.012) analysis. Survivin expression levels were neither associated with patient clinicopathologic characteristics nor with survival. However, expression of survivin in the nucleus was preferentially detected in stage I and II than in stage III and IV (P = 0.007) in the overall series of NSCLC samples. Taken together, our results suggest that aurora B may represent a valid target in NSCLC.
Vischioni
Barbara
B
Division of Medical Oncology, Academic Hospital Vrije Universiteit, 1117 De Boelelaan, HV 1081 Amsterdam, The Netherlands.
Oudejans
Joost J
JJ
Vos
Wim
W
Rodriguez
Jose A
JA
Giaccone
Giuseppe
G
D000328:Adult; D000368:Aged; D064107:Aurora Kinase B; D064127:Aurora Kinases; D001549:Benzamides / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019942:Genes, p16 / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology; D016019:Survival Analysis; D000077022:Survivin; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C474722:4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline; C107489:BIRC5 protein, human; D001549:Benzamides; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011799:Quinazolines; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases