Linked Life Data

19402094

Source:http://linkedlifedata.com/resource/pubmed/id/19402094

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-7-14
pubmed:abstractText
PTEN haploinsufficiency is common in hormone-sensitive prostate cancer, though the incidence of genomic deletion and its downstream effects have not been elucidated in clinical samples of hormone refractory prostate cancer (HRPC). Progression to androgen independence is pivotal in prostate cancer and mediated largely by the androgen receptor (AR). Since this process is distinct from metastatic progression, we examined alterations of the PTEN gene in locally advanced recurrent, non-metastatic human HRPC tissues. Retrospective analyses of PTEN deletion status were correlated with activated downstream phospho-Akt (p-Akt) pathway proteins and with the androgen receptor. The prevalence of PTEN genomic deletions in transurethral resection samples of 59 HRPC patients with known clinical outcome was assessed by four-colour FISH analyses. FISH was performed using six BAC clones spanning both flanking PTEN genomic regions and the PTEN gene locus, and a chromosome 10 centromeric probe. PTEN copy number was also evaluated in a subset of cases using single nucleotide polymorphism (SNP) arrays. In addition, the samples were immunostained with antibodies against p-Akt, p-mTOR, p-70S6, and AR. The PTEN gene was deleted in 77% of cases, with 25% showing homozygous deletions, 18% homozygous and hemizygous deletions, and 34% hemizygous deletions only. In a subset of the study group, SNP array analysis confirmed the FISH findings. PTEN genomic deletion was significantly correlated to the expression of downstream p-Akt (p < 0.0001), AR (p = 0.025), and to cancer-specific mortality (p = 0.039). PTEN deletion is common in HRPC, with bi-allelic loss correlating to disease-specific mortality and associated with Akt and AR deregulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1096-9896
pubmed:author
pubmed:copyrightInfo
(c) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:volume
218
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
505-13
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19402094-Aged, pubmed-meshheading:19402094-Aged, 80 and over, pubmed-meshheading:19402094-Androgen Antagonists, pubmed-meshheading:19402094-Chromosomes, Human, Pair 10, pubmed-meshheading:19402094-Gene Deletion, pubmed-meshheading:19402094-Genome, pubmed-meshheading:19402094-Genotype, pubmed-meshheading:19402094-Humans, pubmed-meshheading:19402094-Immunohistochemistry, pubmed-meshheading:19402094-In Situ Hybridization, Fluorescence, pubmed-meshheading:19402094-Male, pubmed-meshheading:19402094-Middle Aged, pubmed-meshheading:19402094-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19402094-PTEN Phosphohydrolase, pubmed-meshheading:19402094-Phenotype, pubmed-meshheading:19402094-Polymorphism, Single Nucleotide, pubmed-meshheading:19402094-Prostatic Neoplasms, pubmed-meshheading:19402094-Proto-Oncogene Proteins c-akt, pubmed-meshheading:19402094-Receptors, Androgen, pubmed-meshheading:19402094-Signal Transduction, pubmed-meshheading:19402094-Statistics, Nonparametric, pubmed-meshheading:19402094-Treatment Failure
pubmed:year
2009
pubmed:articleTitle
PTEN genomic deletion is associated with p-Akt and AR signalling in poorer outcome, hormone refractory prostate cancer.
pubmed:affiliation
The University of Texas MD Anderson Cancer Center, Department of Pathology, Houston, TX, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't