Linked Life Data

16082189

Source:http://linkedlifedata.com/resource/pubmed/id/16082189

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-11-18
pubmed:abstractText
PAK1, a Rac/CDC42-dependent Ser/Thr kinase, is required for both neurofibromatosis (NF) and RAS transformation in vivo. FK228, a histone deacetylase (HDAC) inhibitor, activates a very specific set of genes such as the tumor suppressor WAF1, an inhibitor of cyclin-dependent kinases (CDKs), and suppresses the growth of these tumors. In addition, this drug downregulates cyclin D1, which is upregulated by RAS through PAK1, in breast cancers. In this study, we demonstrate that FK228 at 0.1-1 nM significantly reduces the kinase activity of PAK1 in these cells, without affecting the protein level of PAK1. Interestingly, estrogen receptor (ER) and PAK1 mutually activate each other in breast cancers. Here we provide an evidence suggesting that breast cancers require PAK1 for their estrogen-dependent growth. Moreover, the treatment with FK228 strongly inhibits the estrogen-dependent growth of human breast cancers (both tamoxifen-sensitive and resistant cell lines) in vivo, suggesting that FK228 and other anti-PAK1 drugs would be useful for the treatment of breast cancers which become resistant to currently used estrogen antagonists such as tamoxifen.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1538-4047
pubmed:author
pubmed:issnType
Print
pubmed:volume
4
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
956-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Signal therapy of breast cancers by the HDAC inhibitor FK228 that blocks the activation of PAK1 and abrogates the tamoxifen-resistance.
pubmed:affiliation
Ludwig Institute for Cancer Research, Parkville/Melbourne, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't