Linked Life Data

16697957

Source:http://linkedlifedata.com/resource/pubmed/id/16697957

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-5-15
pubmed:abstractText
We demonstrate that PTEN loss causes reduced NKX3.1 expression in both murine and human prostate cancers. Restoration of Nkx3.1 expression in vivo in Pten null epithelium leads to decreased cell proliferation, increased cell death, and prevention of tumor initiation. Whereas androgen receptor (AR) positively regulates NKX3.1 expression, NKX3.1 negatively modulates AR transcription and consequently the AR-associated signaling events. Consistent with its tumor suppressor functions, NKX3.1 engages cell cycle and cell death machinery via association with HDAC1, leading to increased p53 acetylation and half-life through MDM2-dependent mechanisms. Importantly, overexpression of Nkx3.1 has little effect on Pten wild-type epithelium, suggesting that PTEN plays a predominant role in PTEN-NKX3.1 interplay. Manipulating NKX3.1 expression may serve as a therapeutic strategy for treating PTEN-deficient prostate cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AR protein, human, http://linkedlifedata.com/resource/pubmed/chemical/HDAC1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 1, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases, http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins, http://linkedlifedata.com/resource/pubmed/chemical/NKX3-1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Nkx3-1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/PTEN Phosphohydrolase, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-mdm2, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Androgen, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1535-6108
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
367-78
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16697957-Acetylation, pubmed-meshheading:16697957-Animals, pubmed-meshheading:16697957-Cell Proliferation, pubmed-meshheading:16697957-Down-Regulation, pubmed-meshheading:16697957-Enzyme Activation, pubmed-meshheading:16697957-Epithelium, pubmed-meshheading:16697957-Gene Expression, pubmed-meshheading:16697957-Histone Deacetylase 1, pubmed-meshheading:16697957-Histone Deacetylases, pubmed-meshheading:16697957-Homeodomain Proteins, pubmed-meshheading:16697957-Humans, pubmed-meshheading:16697957-Male, pubmed-meshheading:16697957-Mice, pubmed-meshheading:16697957-PTEN Phosphohydrolase, pubmed-meshheading:16697957-Promoter Regions, Genetic, pubmed-meshheading:16697957-Prostatic Neoplasms, pubmed-meshheading:16697957-Protein Binding, pubmed-meshheading:16697957-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16697957-Proto-Oncogene Proteins c-mdm2, pubmed-meshheading:16697957-Receptors, Androgen, pubmed-meshheading:16697957-Transcription Factors, pubmed-meshheading:16697957-Transplants, pubmed-meshheading:16697957-Tumor Suppressor Protein p53
pubmed:year
2006
pubmed:articleTitle
NKX3.1 stabilizes p53, inhibits AKT activation, and blocks prostate cancer initiation caused by PTEN loss.
pubmed:affiliation
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural