Linked Life Data

17786040

Source:http://linkedlifedata.com/resource/pubmed/id/17786040

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-1-11
pubmed:abstractText
Farnesyl transferase inhibitors (FTIs) exhibit limited cytotoxic effects against human cancer cells, perhaps explaining the limited efficacy of FTIs in clinical trials. Learning how these well-tolerated drugs trigger p53-independent apoptosis in mouse models of cancer might therefore benefit efforts to leverage their utility in clinic. Recent clinical findings indicate that the oncogenic Rho guanine nucleotide exchange factor AKAP13/Lbc is associated with clinical responsiveness, in support of an earlier genetic proof in mice that gain of the geranylgeranylated isoform of RhoB which blocks oncogenic Rho signaling is essential for FTI-induced apoptosis. Here we offer evidence that the RhoB effector mDia is a critical downstream player in this death program. Dominant inhibition of mDia ablated FTI-induced apoptosis but not actin reorganization or growth inhibition, the latter of which has been linked previously to interactions with a RhoB effector kinase pathway that downregulates c-Myc. In nude mice, dominant inhibition of mDia promoted tumor formation and ablated FTI antitumor efficacy. Our findings suggest that the RhoB-mDia pathway is critical for the cell death mechanism engaged by FTI. Further, they suggest that mDia may be important for Rho-dependent survival of oncogenically transformed cells, perhaps driven by AKAP13/Lbc.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1555-8576
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1422-7
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
mDia function is critical for the cell suicide program triggered by farnesyl transferase inhibition.
pubmed:affiliation
Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural