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

Mol Cancer 2011 Mar 16;10:28. Epub 2011 Mar 16.

Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1186/1476-4598-10-28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068985PMC
March 2011
7 Reads

Publication Analysis

Top Keywords

cell cycle
12
overexpression aurora-a
8
aurora-a primary
8
aurora-a mediated
8
aurora-a
8
cells
5
protein override
4
cyclin protein
4
override aurora-a
4
consequently overexpression
4
cyclin expression
4
expression consequently
4
overexpression cyclin
4
mediated cell
4
cyclin consequence
4
consequence cells
4
cells accumulate
4
influenced cyclin
4
arrest influenced
4
block aurora-a
4

References

(Supplied by CrossRef)

Similar Publications