Linked Life Data

16456618

Source:http://linkedlifedata.com/resource/pubmed/id/16456618

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-3-21
pubmed:abstractText
Missense mutations in the androgen receptor (AR) contribute to the failure of hormonal therapy for prostate cancer (PCa), but the underlying molecular bases remain uncharacterized. Here, we describe a new AR variant found in a hormone-refractory metastatic PCa, in which threonine 575 in the DNA binding domain, and threonine 877 in the ligand-binding domain, were both replaced by an alanine. Using gene reporter assays, we demonstrate that the T575A mutation weakened transcriptional activity from promoters containing AR-specific responsive elements, while activity from promoters with AR-non-specific elements was enhanced. Data from gel shift experiments revealed a preferential binding of the T575A mutant to AR-non-specific motifs. We demonstrate that the two mutations T575A and T877A cooperate to confer new functional properties on the AR, and that the mutant AR functions simultaneously as a promiscuous AR due to the T877A mutation, and an unfaithful AR due to the T575A mutation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1420-682X
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
487-97
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Unfaithfulness and promiscuity of a mutant androgen receptor in a hormone-refractory prostate cancer.
pubmed:affiliation
Laboratoire de Cancérologie Expérimentale et de Radiobiologie, EA 3430, Université Louis Pasteur de Strasbourg, IRCAD, BP426, Strasbourg Cedex, 67091, France.
pubmed:publicationType
Journal Article