Linked Life Data

20861223

Source:http://linkedlifedata.com/resource/pubmed/id/20861223

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-10-28
pubmed:abstractText
Cotreatment with testosterone (T) and 17?-estradiol (E2) is an established regimen for inducing of prostatic intraepithelial neoplasia (PIN) and prostate cancer in rodent models. We previously used the pure antiestrogen ICI 182,780 (ICI) and bromocriptine, a dopamine receptor agonist, to inhibit PIN induction and systemic hyperprolactinemia in Noble rats and found that the carcinogenic action of T+E2 is mediated directly by the effects of E2 on the prostate and/or indirectly via E2-induced hyperprolactinemia. In this study, we delineate the specific action(s) of E2 and prolactin (PRL) in early prostate carcinogenesis by an integrated approach combining global transcription profiling, gene ontology, and gene-network mapping. We identified 2504 differentially expressed genes in the T+E2-treated lateral prostate. The changes in expression of a subset of 1990 genes (?80%) were blocked upon cotreatment with ICI and bromocriptine, respectively, whereas those of 262 genes (?10%) were blocked only by treatment with ICI, suggesting that E2-induced pituitary PRL is the primary mediator of the prostatic transcriptional response to the altered hormone milieu. Bioinformatics analyses identified hormone-responsive gene networks involved in immune responses, stromal tissue remodeling, and the ERK pathway. In particular, our data suggest that IL-1? may mediate, at least in part, hormone-induced changes in gene expression during PIN formation. Together, these data highlight the importance of pituitary PRL in estrogen-induced prostate tumorigenesis. The identification of both E2- and pituitary PRL-responsive genes provides a comprehensive resource for future investigations of the complex mechanisms by which changes in the endocrine milieu contribute to prostate carcinogenesis in vivo.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1944-9917
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2207-17
pubmed:dateRevised
2011-11-1
pubmed:meshHeading
pubmed-meshheading:20861223-Animals, pubmed-meshheading:20861223-Bromocriptine, pubmed-meshheading:20861223-Calgranulin B, pubmed-meshheading:20861223-Cell Proliferation, pubmed-meshheading:20861223-Chemokine CXCL13, pubmed-meshheading:20861223-Epithelial Cells, pubmed-meshheading:20861223-Estradiol, pubmed-meshheading:20861223-Gene Expression Regulation, Neoplastic, pubmed-meshheading:20861223-Gene Regulatory Networks, pubmed-meshheading:20861223-Interleukin-1beta, pubmed-meshheading:20861223-Male, pubmed-meshheading:20861223-Prolactin, pubmed-meshheading:20861223-Prostate, pubmed-meshheading:20861223-Prostatic Intraepithelial Neoplasia, pubmed-meshheading:20861223-Prostatic Neoplasms, pubmed-meshheading:20861223-Rats, pubmed-meshheading:20861223-Reproducibility of Results, pubmed-meshheading:20861223-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20861223-Testosterone
pubmed:year
2010
pubmed:articleTitle
Research resource: estrogen-driven prolactin-mediated gene-expression networks in hormone-induced prostatic intraepithelial neoplasia.
pubmed:affiliation
Department of Environmental Health, University of Cincinnati Medical Center, Kettering Laboratory, Suite 128, 3223 Eden Avenue, Cincinnati, Ohio 45267-0056, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural