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Molecular Cancer
Published in: Molecular Cancer 1/2011

Open Access 01-12-2011 | Research

Overexpression of Aurora-A in primary cells interferes with S-phase entry by diminishing Cyclin D1 dependent activities

Authors: Florian Jantscher, Christine Pirker, Christoph-Erik Mayer, Walter Berger, Hedwig Sutterluety

Published in: Molecular Cancer | Issue 1/2011

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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.

Conclusion

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.
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Metadata
Title
Overexpression of Aurora-A in primary cells interferes with S-phase entry by diminishing Cyclin D1 dependent activities
Authors
Florian Jantscher
Christine Pirker
Christoph-Erik Mayer
Walter Berger
Hedwig Sutterluety
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2011
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-10-28

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