Frequent overexpression of aurora B kinase, a novel drug target, in non-small cell lung carcinoma patients

Mol Cancer Ther. 2006 Nov;5(11):2905-13. doi: 10.1158/1535-7163.MCT-06-0301.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aurora Kinase B
  • Aurora Kinases
  • Benzamides / pharmacology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Genes, p16 / physiology
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology*
  • Male
  • Microtubule-Associated Proteins / metabolism
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / metabolism*
  • Quinazolines / pharmacology
  • Survival Analysis
  • Survivin
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • 4-(4-(N-benzoylamino)anilino)-6-methoxy-7-(3-(1-morpholino)propoxy)quinazoline
  • BIRC5 protein, human
  • Benzamides
  • Cyclin-Dependent Kinase Inhibitor p16
  • Enzyme Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Quinazolines
  • Survivin
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases