Linked Life Data

21217774

Source:http://linkedlifedata.com/resource/pubmed/id/21217774

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-4-28
pubmed:abstractText
Estrogen receptor alpha (ER?) is a ligand-dependent nuclear receptor that is important in breast cancer genesis, behavior and response to hormone-based therapies. A T7 phage display screen against full-length human ER?, coupled with genome-wide exon arrays, was used to identify RAC3 as a putative ER? co-regulator. RAC3 is a Rho family small GTPase that is associated with cytoskeletal rearrangement. We demonstrate a novel role for nuclear RAC3 as an ER? transcriptional activator, with prognostic implications for metastatic disease. Through in vitro and cell-based studies, RAC3 was shown to exist in a GTP-bound state and act as a ligand specific ER? co-activator of E2-induced transcription. Overexpression of RAC3 induced pro-growth and pro-migratory genes that resulted in increased migration of ER?-positive breast cancer cells. Chemical inhibition and genetic knockdown of RAC3 antagonized E2-induced cell proliferation, cell migration and ER? mediated gene expression, indicating that RAC3 is necessary for full ER? transcriptional activity. In agreement with the molecular and cellular data, RAC3 overexpression in ER?-positive breast cancers correlated with a significant decrease in recurrence free survival and a significant increase in the odds ratio of metastasis. In conclusion, RAC3 is a novel ER? co-activator that promotes cell migration and has prognostic value for ER?-positive breast cancer metastasis. RAC3 may also be a useful therapeutic target for ER?-positive breast cancers.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
28
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1984-94
pubmed:dateRevised
2011-10-28
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
RAC3 is a pro-migratory co-activator of ER?.
pubmed:affiliation
University of Chicago, Committee on Cancer Biology, Chicago, IL 60637, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural