Linked Life Data

17550981

Source:http://linkedlifedata.com/resource/pubmed/id/17550981

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-8-28
pubmed:abstractText
Androgen receptor (AR) plays an important role in normal prostate function as well as in the etiology of prostate cancer. Activation of AR is dictated by hormone binding and by interactions with coregulators. Several of these coregulators are known targets of Ras-related signals. Recent evidence suggests that Ras activation may play a causal role in the progression of prostate cancer toward a more malignant and hormone-insensitive phenotype. In the present study, we used a transcription factor-transcription factor interaction array method to identify the zinc finger protein Ras-responsive element binding protein (RREB-1) as a partner and coregulator of AR. In LNCaP prostate cancer cells, RREB-1 was found to be present in a complex with endogenous AR as determined by coimmunoprecipitation, glutathione S-transferase pull down, and immunofluorescence analyses. RREB-1 bound to the prostate-specific antigen (PSA) promoter as assessed by chromatin immunoprecipitation. Transient expression of RREB-1 down-regulated AR-mediated promoter activity and suppressed expression of PSA protein. The repressor activity of RREB-1 was significantly attenuated by cotransfection of activated Ras. Moreover, expression of the dominant-negative N-17-Ras or, alternatively, use of the MAPK kinase inhibitor PD98059 [2-(2-amino-3-methyoxyphenyl)-4H-1-benzopyran-4-one] abolished the effect of Ras in attenuating RREB-1-mediated repression. Furthermore, inhibition of RREB-1 expression by RNA interference enhanced the effect of Ras on PSA promoter activity and PSA expression. In addition, activation of the Ras pathway depleted AR from the RREB-1/AR complex. Collectively, our data for the first time identify RREB-1 as a repressor of AR and further implicate the Ras/MAPK kinase pathway as a likely antagonist of the inhibitory effects of RREB-1 on androgenic signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2056-70
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
The zinc finger protein ras-responsive element binding protein-1 is a coregulator of the androgen receptor: implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer.
pubmed:affiliation
Department of Urology/Surgery, Children's Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. nishit.mukhopadhyay@childrens.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural