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Pleomorphic adenoma gene-like 2 regulates expression of the p53 family member, p73, and induces cell cycle block and apoptosis in human promonocytic U937 cells.
MedLine Citation:
PMID:  22076304     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The proto-oncogene, pleomorphic adenoma gene-like 2 (PLAGL2), is implicated in a variety of cancers including acute myeloid leukemia (AML), malignant glioma, colon cancer, and lung adenocarcinoma. There is additional evidence that PLAGL2 can function as a tumor suppressor by initiating cell cycle arrest and apoptosis. Interestingly, PLAGL2 has also been implicated in human myelodysplastic syndrome, a disease that is characterized by ineffective hematopoiesis and can lead to fatal cytopenias (low blood counts) as a result of increased apoptosis in the marrow, or, in about one-third of cases, can progress to AML. To gain a better understanding of the actions of PLAGL2 in human myeloid cells, we generated a stable PLAGL2-inducible cell line, using human promonocytic U937 cells. PLAGL2 expression inhibited cell proliferation which correlated with an accumulation of cells in G1, apoptotic DNA-laddering, an increase in caspase 3, 8, and 9 activity, and a loss of mitochondrial transmembrane potential. There was significant increase in the p53 homologue, p73, with PLAGL2 expression, and consistent with mechanisms of p73-regulated cell cycle control and apoptosis, there was increased expression of known p73 target genes p21, DR5, TRAIL, and Bax. PLAGL2-induced cell cycle block was abolished in the presence of p73 siRNA. Together, these data support a role for PLAGL2 in cell cycle regulation and apoptosis via activation of p73.
Authors:
Tracey S Hanks; Katherine A Gauss
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-11
Journal Detail:
Title:  Apoptosis : an international journal on programmed cell death     Volume:  -     ISSN:  1573-675X     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9712129     Medline TA:  Apoptosis     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Immunology and Infectious Diseases, Montana State University, 960 Technology Blvd., Bozeman, MT, 59718, USA.
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