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Blood, 1 January 2006, Vol. 107, No. 1, pp. 250-256.
Prepublished online as a Blood First Edition Paper on September 13, 2005; DOI 10.1182/blood-2005-03-1194.
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Submitted March 24, 2005
Accepted August 12, 2005
Transcriptional silencing of Polo-like Kinase 2 (Snk/Plk2) is a frequent event in B cell malignancies
Nelofer Syed, Paul Smith, Alexandra Sullivan, Lindsay C Spender, Martin Dyer, Lorraine Karran, Jenny O'Nions, Martin Allday, Ingrid Hoffmann, Dorothy Crawford, Beverley Griffin, Paul J Farrell, and Tim Crook*
Breakthrough Breast Cancer Centre, Institute for Cancer Research, London, United Kingdom
Ludwig Institute for Cancer Research, University College London, London, United Kingdom
Beatson Institute for Cancer Research, Growth Factor Signalling Laboratory, Glasgow, United Kingdom
MRC Toxicology Unit, University of Leicester Medical School, Leicester, United Kingdom
Department of Virology, Imperial College Faculty of Medicine, St. Mary's Campus, London, United Kingdom
Cell Cycle Control and Carcinogenesis, German Cancer Research Center DKFZ, Heidelberg, Germany
Department of Veterinary Pathology, University of Edinburgh, Edinburgh, United Kingdom
* Corresponding author; email: t.crook{at}ic.ac.uk.
The Polo-like Kinases (Plks) are a highly conserved family of protein kinases that function in regulation of cell cycle and DNA damage-induced checkpoints. Evidence of a tumor suppressor function for the Plks in human neoplasia is lacking. Here, we report that Snk/Plk2 is transcriptionally down regulated in B cell neoplasia. Down regulation occurs with high frequency in Burkitt's lymphoma (BL), but is also detected in B cell neoplasms of other types and is associated with aberrant cytosine methylation in the CpG island located at the 5' end of the Snk/Plk2 gene. Silencing is specific to malignant B cells because Snk/Plk2 was unmethylated (and expressed) in primary B lymphocytes, in EBV-immortalised B lymphoblastoid cell lines (LCLs) and in adenocarcinomas (of the breast) and squamous cell carcinomas (of the head and neck). Expression of Snk/Plk2 in BL cell lines was restored by demethylating agents. The related Plk1 and Plk3 (Fnk/Prk) genes were over-expressed in BL cell lines lacking Snk/Plk2 expression, consistent with functional degeneracy among the Plk family. Ectopic expression of Snk/Plk2 in BL cells resulted in apoptosis, a potential mechanistic basis underlying the strong selective pressure for abrogation of Snk/Plk2 function in B cell neoplasia.
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