title: Overexpression of Aurora-A in primary cells interferes with S-phase entry by diminishing Cyclin D1 dependent activities.
abstract: BACKGROUND
  Aurora-A is a bona-fide oncogene whose expression is associated with genomic instability and malignant transformation. In several types of cancer, gene amplification and/or increased protein levels of Aurora-A are a common feature.
  
  
  RESULTS
  In this report, we describe that inhibition of cell proliferation is the main effect observed after transient overexpression of Aurora-A in primary human cells. In addition to the known cell cycle block at the G2/M transition, Aurora-A overexpressing cells fail to overcome the restriction point at the G1/S transition due to diminished RB phosphorylation caused by reduced Cyclin D1 expression. Consequently, overexpression of Cyclin D1 protein is able to override the Aurora-A mediated G1 block. The Aurora-A mediated cell cycle arrest in G2 is not influenced by Cyclin D1 and as a consequence cells accumulate in G2. Upon deactivation of p53 part of the cells evade this premitotic arrest to become aneuploid.
  
  
  CONCLUSIONS
  Our studies describe that an increase of Aurora-A expression levels on its own has a tumor suppressing function, but in combination with the appropriate altered intracellular setting it might exert its oncogenic potential. The presented data indicate that deactivation of the tumor suppressor RB is one of the requirements for overriding a cell cycle checkpoint triggered by increased Aurora-A levels.
authors.affiliation: Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Jantscher
authors.forename: Christine
authors.initials: C
authors.lastname: Pirker
authors.forename: Christoph-Erik
authors.initials: CE
authors.lastname: Mayer
authors.forename: Walter
authors.initials: W
authors.lastname: Berger
authors.forename: Hedwig
authors.initials: H
authors.lastname: Sutterluety
mesh_terms: D064127:Aurora Kinases; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism*; D016193:G1 Phase; D005786:Gene Expression Regulation; D006801:Humans; D008938:Mitosis; D050505:Mutant Proteins; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: C530104:CCND1 protein, human; D050505:Mutant Proteins; C411762:RASSF1 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D020703:ras GTPase-Activating Proteins; D019938:Cyclin D1; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases