Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-12-25
pubmed:abstractText
Treatment of H-Ras transgenic mice with the geranylgeranyltransferase I (GGTase I) inhibitor GGTI-2154 results not only in halting the growth of aggressive breast tumors but actually in inducing the regression (54 +/- 3%) of all 19 tumors analyzed. The farnesyltransferase (FTase) inhibitor FTI-2148 induced an average of 87 +/- 3% regression in the 13 tumors analyzed. GGTase I, but not FTase, is inhibited in breast tumors after treatment with GGTI-2154, whereas in tumors from mice treated with FTI-2148, only FTase is inhibited. The processing of the geranylgeranylated proteins RhoA, Rap1, and R-Ras, but not the farnesylated proteins H-Ras and HDJ-2, is inhibited in tumors obtained from mice treated with GGTI-2154. GGTI-2154 and FTI-2148 suppress constitutively activated phospho-Erk1/2 and phospho-Akt, induce apoptosis, and induce differentiation toward ductolobular breast epithelium. The data demonstrate that geranylgeranylated proteins are critical in H-Ras oncogenesis in vivo and give strong support for GGTase I as a target for anticancer drug discovery.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alkyl and Aryl Transferases, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNAJA1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases, http://linkedlifedata.com/resource/pubmed/chemical/HSP40 Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles, http://linkedlifedata.com/resource/pubmed/chemical/Rras protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/geranylgeranyltransferase type-I, http://linkedlifedata.com/resource/pubmed/chemical/p21(ras) farnesyl-protein..., http://linkedlifedata.com/resource/pubmed/chemical/rap1 GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins, http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8922-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14695209-Alkyl and Aryl Transferases, pubmed-meshheading:14695209-Animals, pubmed-meshheading:14695209-Apoptosis, pubmed-meshheading:14695209-Carrier Proteins, pubmed-meshheading:14695209-Cell Differentiation, pubmed-meshheading:14695209-Cell Transformation, Neoplastic, pubmed-meshheading:14695209-Enzyme Inhibitors, pubmed-meshheading:14695209-GTP Phosphohydrolases, pubmed-meshheading:14695209-Genes, ras, pubmed-meshheading:14695209-HSP40 Heat-Shock Proteins, pubmed-meshheading:14695209-Heat-Shock Proteins, pubmed-meshheading:14695209-Imidazoles, pubmed-meshheading:14695209-Mammary Neoplasms, Experimental, pubmed-meshheading:14695209-Mammary Tumor Virus, Mouse, pubmed-meshheading:14695209-Mice, pubmed-meshheading:14695209-Mice, Transgenic, pubmed-meshheading:14695209-Necrosis, pubmed-meshheading:14695209-rap1 GTP-Binding Proteins, pubmed-meshheading:14695209-ras Proteins, pubmed-meshheading:14695209-rhoA GTP-Binding Protein
pubmed:year
2003
pubmed:articleTitle
Geranylgeranyltransferase I inhibitor GGTI-2154 induces breast carcinoma apoptosis and tumor regression in H-Ras transgenic mice.
pubmed:affiliation
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida 33612, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.