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RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

Oncogene volume 26, pages 683–700 (2007)Cite this article

Abstract

We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine–threonine kinase that signals downstream of the mitogen-activated protein kinase pathway. It is expressed in normal ovarian epithelium, whereas reduced or absent in tumours or cell lines. We show that RPS6KA2 is monoallelically expressed in the ovary suggesting that loss of a single expressed allele is sufficient to cause complete loss of expression in cancer cells. Further, we have identified two new isoforms of RPS6KA2 with an alternative start codon. Homozygous deletions were identified within the RPS6KA2 gene in two cell lines. Re-expression of RPS6KA2 in ovarian cancer cell lines suppressed colony formation. In UCI101 cells, the expression of RPS6KA2 reduced proliferation, caused G1 arrest, increased apoptosis, reduced levels of phosphorylated extracellular signal-regulated kinase and altered other cell cycle proteins. In contrast, small interfering RNA against RPS6KA2 showed the opposite effect in 41M cells. The above results suggest that RPS6KA2 is a putative tumour suppressor gene to explain allele loss at 6q27.

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Acknowledgements

Dr Iain Goldsmith is acknowledged for synthesis of oligonucleotides, Mr Reginald Boone, Dr Anna Richardson and Kevin Clark for assistance with sequencing. Dr S Manek reviewed the pathology and some tumour specimens were obtained from Mr I Mackenzie and Mr M Gillmer. The sequence analysis of PAC/BAC was performed with the assistance of Dr Brooksbank. We thank all members of the chromosome 6 project group at the Sanger Centre. We also thank all the past and present members of the Ovarian Cancer Group for their generous and unique assistance. The work described in this paper is supported by the Cancer Research UK, Association of International Cancer Research, Wellbeing and Human mapping/sequencing at the Sanger Centre is funded by the Wellcome Trust.

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  1. T S Ganesan

    Present address: Cancer Institute and Institute of Molecular Medicine, Amrita Institute of Medical Sciences, Elamakkara PO, Cochin, 682026, India

  2. P A Bignone and K Y Lee: These authors contributed equally to this work.

Authors and Affiliations

  1. Cancer Research UK, Molecular Oncology Laboratories, Ovarian Cancer Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK

    P A Bignone, K Y Lee, Y Liu, G Emilion, J Finch, A E R Soosay, F M L Charnock & T S Ganesan

  2. The Sanger Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    S Beck, I Dunham & A J Mungall

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Bignone, P., Lee, K., Liu, Y. et al. RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer. Oncogene 26, 683–700 (2007). https://doi.org/10.1038/sj.onc.1209827

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