Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype

doi:10.1186/1471-2407-7-212

BMC Cancer
Volume 7

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Amato A
Schillaci T
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Research article

Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype

Laura Lentini¹ , Angela Amato¹ , Tiziana Schillaci¹ and Aldo Di Leonardo¹^,2

¹Department of Cellular and Developmental Biology "A. Monroy", University of Palermo, viale delle Scienze, Palermo, Italy

²Centro di OncoBiologia Sperimentale, via San Lorenzo 312, Palermo, Italy

author email corresponding author email

BMC Cancer 2007, 7:212doi:10.1186/1471-2407-7-212


Published:	13 November 2007

Abstract

Background

Genetic instability is a hallmark of tumours and preneoplastic lesions. The predominant form of genome instability in human cancer is chromosome instability (CIN). CIN is characterized by chromosomal aberrations, gains or losses of whole chromosomes (aneuploidy), and it is often associated with centrosome amplification. Centrosomes control cell division by forming a bipolar mitotic spindle and play an essential role in the maintenance of chromosomal stability.

However, whether centrosome amplification could directly cause aneuploidy is not fully established. Also, alterations in genes required for mitotic progression could be involved in CIN.

A major candidate is represented by Aurora-A/STK15 that associates with centrosomes and is overexpressed in several types of human tumour.

Methods

Centrosome amplification were induced by hydroxyurea treatment and visualized by immunofluorescence microscopy. Aurora-A/STK15 ectopic expression was achieved by retroviral infection and puromycin selection in HCT116 tumour cells. Effects of Aurora-A/STK15 depletion on centrosome status and ploidy were determined by Aurora-A/STK15 transcriptional silencing by RNA interference. Changes in the expression levels of some mitotic genes were determined by Real time RT-PCR.

Results

We investigated whether amplification of centrosomes and overexpression of Aurora-A/STK15 induce CIN using as a model system a colon carcinoma cell line (HCT116). We found that in HCT116 cells, chromosomally stable and near diploid cells harbouring a MIN phenotype, centrosome amplification induced by hydroxyurea treatment is neither maintained nor induces aneuploidy. On the contrary, ectopic overexpression of Aurora-A/STK15 induced supernumerary centrosomes and aneuploidy. Aurora-A/STK15 transcriptional silencing by RNA interference in cells ectopically overexpressing this kinase promptly decreased cell numbers with supernumerary centrosomes and aneuploidy.

Conclusion

Our results show that centrosome amplification alone is not sufficient to induce chromosomal instability in colon cancer cells with a MIN phenotype. Alternatively, centrosome amplification has to be associated with alterations in genes regulating mitosis progression such as Aurora-A/STK15 to trigger CIN.