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DBC1 re-expression alters the expression of multiple components of the plasminogen pathway

Oncogene volume 25, pages 2409–2419 (2006)Cite this article

Abstract

Deleted in bladder cancer 1 (DBC1) is a candidate gene for the bladder tumour suppressor locus at 9q33.1. The function of the gene is currently unknown but a cross-species sequence comparison suggests an important role, as it is highly evolutionarily conserved. Here, we transfected a nonexpressing human bladder cancer cell line with a set of human DBC1 cDNA constructs. The effect on global expression patterns was assessed using cDNA microarrays. The cell clone with the lowest level of DBC1 expression showed induced expression of 26 genes including plasminogen activator inhibitor 2 (SERPINB5; 4.6-fold), heparin-binding EGF-like growth factor precursor (DTR; 4.2-fold), small proline-rich protein 2B (SPRR2B; 3.6-fold), metallothionein 1 isoforms (MT1B/MT1A/MT-1F; from 2.9- to 3.2-fold), tissue-type plasminogen activator precursor (PLAT; 2.8-fold) and urokinase-type plasminogen activator precursor (PLAU; 2.7-fold). In clustering analysis, both PLAT and PLAU clustered with the functionally related urokinase plasminogen activator surface receptor (PLAUR; 1.9-fold). Furthermore, 14 human bladder tumours were analysed by real-time quantitative PCR using gene-specific primers for selected (n=20) genes. The expression levels of SERPINB5, PLAU, PLAUR and MT1 correlated with the DBC1 levels, suggesting previously unknown involvement of DBC1 in the urokinase-plasminogen pathway.

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Acknowledgements

This research was supported by Cancer Research UK. We thank the staff of the Sanger Institute Microarray Facility for the supply of arrays, lab protocols, and technical advice (David Vetrie, Cordelia Langford, Adam Whittaker, Neil Sutton), Quantarray/GeneSpring datafiles and all data analysis and databases relating to elements on the arrays (Kate Rice, Rob Andrews, Adam Butler, Harish Chudasama). The microarray consortium is funded by the Wellcome Trust, Cancer Research UK and the Ludwig Institutes of Cancer Research. The human IMAGE cDNA clone collection was obtained from the MRC HGMP Resource Centre (Hinxton, UK). All cDNA clone resequencing was performed by Team 56 at the Sanger Institute. We also appreciate the help extended by Simon Tomlinson from Cancer Research UK in London.

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  1. Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, West Yorkshire, UK

    J P Louhelainen, C D Hurst, E Pitt, H Nishiyama, H A Pickett & M A Knowles

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  1. J P Louhelainen
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Correspondence to M A Knowles.

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Louhelainen, J., Hurst, C., Pitt, E. et al. DBC1 re-expression alters the expression of multiple components of the plasminogen pathway. Oncogene 25, 2409–2419 (2006). https://doi.org/10.1038/sj.onc.1209228

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