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HACE1 is a tumor suppressor gene candidate in natural killer cell neoplasms.
- Source :
-
The American journal of pathology [Am J Pathol] 2013 Jan; Vol. 182 (1), pp. 49-55. Date of Electronic Publication: 2012 Nov 09. - Publication Year :
- 2013
-
Abstract
- HACE1 is an E3 ubiquitin ligase located in 6q21, the genomic region frequently deleted in natural killer (NK) cell malignancies. Here, we report HACE1 as a candidate tumor suppressor gene silenced through a combination of deletion and cytosine phosphate guanine island hypermethylation. We detected deletion of HACE1 in malignant NK cell lines (6 of 9, 67%) and primary biopsies (5 of 15, 33%) by quantitative PCR, with most of the specimen showing cytosine phosphate guanine island hypermethylation in the remaining allele, leading to low mRNA transcription. The ectopic expression of HACE1 in an HACE1-null NK cell line led to apoptosis and G2/M cell cycle arrest. Moreover, HACE1 expression was up-regulated in IL-2-activated normal NK cells and NK cells cocultured with an engineered NK cell target, K562 Clone 9.mbIL21, suggesting its role in the regulation of NK cell homeostasis. In conclusion, HACE1 is another potent tumor suppressor gene located within the 6q21 region, and loss of function of multiple tumor suppressor genes within 6q21 may be a critical determinant of NK cell lymphomagenesis.<br /> (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Apoptosis genetics
Cell Cycle Checkpoints genetics
Coculture Techniques
CpG Islands genetics
DNA Methylation
DNA Mutational Analysis methods
DNA, Neoplasm genetics
Gene Deletion
Gene Expression Regulation, Neoplastic
Gene Silencing
Genes, Tumor Suppressor
Humans
Interleukin-2 immunology
Killer Cells, Natural immunology
Killer Cells, Natural pathology
Lymphocyte Activation genetics
Lymphoma, Non-Hodgkin metabolism
Lymphoma, Non-Hodgkin pathology
Tumor Cells, Cultured
Ubiquitin-Protein Ligases biosynthesis
Up-Regulation genetics
Killer Cells, Natural metabolism
Lymphoma, Non-Hodgkin genetics
Ubiquitin-Protein Ligases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 182
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23142381
- Full Text :
- https://doi.org/10.1016/j.ajpath.2012.09.012