Abstract
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 neoplasms. Silencing occurs with very high frequency in Burkitt 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-immortalized 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 overexpressed 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.
Original language | English |
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Pages (from-to) | 250-256 |
Number of pages | 7 |
Journal | Blood |
Volume | 107 |
Issue number | 1 |
Early online date | 22 Dec 2005 |
DOIs | |
Publication status | Published - 1 Jan 2006 |
Keywords
- Apoptosis
- B-Lymphocytes
- Cell Cycle Proteins
- DNA Methylation
- Gene Expression Regulation, Neoplastic
- Gene Silencing
- Humans
- Leukemia, B-Cell
- Lymphoma, B-Cell
- Protein-Serine-Threonine Kinases
- Proto-Oncogene Proteins
- Transcription, Genetic
- Tumor Cells, Cultured
- Journal Article
- Research Support, Non-U.S. Gov't