title: Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation.
abstract: BACKGROUND
  Chromosomal instability is one of the most common features of prostate cancer (PC), especially in advanced stages. Recent studies suggest that defects in mitotic checkpoints play a role in carcinogenesis. Lack of mitotic regulation induces aneuploidy in cancer cells acting thereafter as a driving force for malignant progression. Serine/threonine protein kinases of the Aurora genes family play an important throughout the entire cell cycle. In that Aurora B regulates chromosome segregation by ensuring the orientation of sister chromatids. As a consequence, the overexpression of Aurora B in diploid human cells NHDF induces the appearance of multinucleate cells.
  
  
  METHODS
  Archive samples of normal and neoplastic prostate tissue, and prostate derived cell lines were screened for the expression of Aurora B.
  
  
  RESULTS
  Immunohistochemical analysis showed increased nuclear expression of Aurora-B in high Gleason grade PCs respect to low and intermediate grade cases and in all cancers in respect to hyperplastic and normal glands. Furthermore, in the high Gleason grade anaplastic cancer tissues Aurora B expression was accompanied by the phosphorylation of the histone H3. In analogy to the in vivo situation, Aurora B was vigorously expressed in the androgen independent PC cell lines PC3 and DU145, while a very modest expression of the kinase was observed in the androgen sensitive LnCap cells and in the EPN cells, a line of epithelial cells derived from normal prostate tissue. In addition, in PC3 cells Aurora B expression is accompanied the by the phosphorylation of the histone H3. The block of Aurora B expression induced by an inhibitor of Aurora kinase activity significantly reduced the growth of prostate carcinoma cells, but not that of non-transformed EPN cells.
  
  
  CONCLUSIONS
  Our data are the first demonstration of a role of Aurora B in PC progression. In addition, the observation that Aurora B specific inhibitors interfere with PC cell proliferation but not with that of non-transformed prostate epithelial cells suggest that Aurora B is a potential therapeutic target for PC.
authors.affiliation: Dipartimento di Medicina Sperimentale, II Università di Napoli, Naples, Italy. Paolo.Chieffi@unina2.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Chieffi
authors.forename: Laura
authors.initials: L
authors.lastname: Cozzolino
authors.forename: Annamaria
authors.initials: A
authors.lastname: Kisslinger
authors.forename: Silvana
authors.initials: S
authors.lastname: Libertini
authors.forename: Stefania
authors.initials: S
authors.lastname: Staibano
authors.forename: Gelsomina
authors.initials: G
authors.lastname: Mansueto
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Rosa
authors.forename: Antonia
authors.initials: A
authors.lastname: Villacci
authors.forename: Mario
authors.initials: M
authors.lastname: Vitale
authors.forename: Spiros
authors.initials: S
authors.lastname: Linardopoulos
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Portella
authors.forename: Donatella
authors.initials: D
authors.lastname: Tramontano
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000201:enzymology* / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011799:Quinazolines / Q000494:pharmacology
chemical_list: D006657:Histones; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases