Linked Life Data

13679438

Source:http://linkedlifedata.com/resource/pubmed/id/13679438

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-9-18
pubmed:abstractText
Androgens play a key role in the regulation of the normal prostate as well as in the promotion and progression of prostate cancer. Recently, an oncogenic serine/threonine kinase, Pim-1, was reported to be overexpressed in prostate cancer. To elucidate whether Pim-1 is capable of modulating androgen signaling, we studied the effects of Pim-1 on androgen receptor (AR)-dependent transcription. Under transient transfection conditions, Pim-1 attenuated transcriptional activity of AR in a dose-dependent fashion in PC-3, HeLa, and COS-1 cells, whereas a kinase-negative mutant of Pim-1, Pim-1(K67M), showed no repressive activity. In contrast, ectopic expression of Pim-1 did not influence the activity of endogenous AR in LNCaP cells. This was, however, not a result of the T877A mutation present in AR of LNCaP cells, because that AR mutant was repressed by Pim-1 as efficiently as wild-type AR when expressed in PC-3 prostate cancer cells. Pim-1 inhibited AR mutants devoid of the ligand-binding domain or the core amino-terminal transactivation function but failed to influence the DNA binding of AR. Because we found no evidence for phosphorylation of AR by Pim-1 or for direct interaction between these proteins, Pim-1 is likely to influence AR activity via an indirect mechanism, possibly involving phosphorylation of a coregulator and/or a component of the transcription machinery. Overexpression of Pim-1 may thus attenuate androgen response during progression of prostate cancer in a cell context-dependent fashion.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
83
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1301-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Attenuation of androgen receptor-dependent transcription by the serine/threonine kinase Pim-1.
pubmed:affiliation
Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't