Abstract |
hnRNP K regulates cellular programs, and changes in its expression and mutational status have been implicated in neoplastic malignancies. To directly examine its role in tumorigenesis, we generated a mouse model harboring an Hnrnpk knockout allele (Hnrnpk(+/-)). Hnrnpk haploinsufficiency resulted in reduced survival, increased tumor formation, genomic instability, and the development of transplantable hematopoietic neoplasms with myeloproliferation. Reduced hnRNP K expression attenuated p21 activation, downregulated C/EBP levels, and activated STAT3 signaling. Additionally, analysis of samples from primary acute myeloid leukemia patients harboring a partial deletion of chromosome 9 revealed a significant decrease in HNRNPK expression. Together, these data implicate hnRNP K in the development of hematological disorders and suggest hnRNP K acts as a tumor suppressor.
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Authors | Miguel Gallardo, Hun Ju Lee, Xiaorui Zhang, Carlos Bueso-Ramos, Laura R Pageon, Mark McArthur, Asha Multani, Aziz Nazha, Taghi Manshouri, Jan Parker-Thornburg, Inmaculada Rapado, Alfonso Quintas-Cardama, Steven M Kornblau, Joaquin Martinez-Lopez, Sean M Post |
Journal | Cancer cell
(Cancer Cell)
Vol. 28
Issue 4
Pg. 486-499
(Oct 12 2015)
ISSN: 1878-3686 [Electronic] United States |
PMID | 26412324
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- HNRNPK protein, mouse
- Heterogeneous-Nuclear Ribonucleoprotein K
- Ribonucleoproteins
- HNRNPK protein, human
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Topics |
- Animals
- Cell Differentiation
- Cell Proliferation
- Cells, Cultured
- Chromosomal Instability
- Chromosomes, Human, Pair 9
(genetics)
- Gene Expression Regulation, Neoplastic
- Gene Knockout Techniques
- Haploinsufficiency
- Hematologic Neoplasms
(genetics, metabolism, pathology)
- Heterogeneous-Nuclear Ribonucleoprotein K
- Humans
- Mice
- Ribonucleoproteins
(genetics, metabolism)
- Signal Transduction
- Survival Analysis
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