Journal
BLOOD
Volume 107, Issue 1, Pages 250-256Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-03-1194
Keywords
-
Categories
Funding
- MRC [MC_U132670597] Funding Source: UKRI
- Medical Research Council [MC_U132670597] Funding Source: Medline
- Breast Cancer Now [BREAST CANCER NOW RESEARCH CENTRE] Funding Source: Medline
Ask authors/readers for more resources
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 BIL cells resulted in apoptosis, a potential mechanistic basis underlying the strong selective pressure for abrogation of Snk/Plk2 function in B-cell neoplasia.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available