Linked Life Data

17974981

Source:http://linkedlifedata.com/resource/pubmed/id/17974981

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2007-11-2
pubmed:abstractText
The fragile histidine triad (FHIT) gene has been shown to function as a tumor suppressor gene in vitro and in vivo. However, the mechanism of its action is still largely unknown. To elucidate the molecular mechanism and biological pathway in FHIT-mediated tumor suppression, we used a complementary gene and protein expression profiling with DNA microarray and ProteinChip technologies to quantitatively monitor cellular changes in gene and protein expression and discover the molecular targets of FHIT in non-small cell lung carcinoma (NSCLC) cells. The Ras/Rho signaling pathway was identified as one of the unique biological pathways associated with FHIT activity. A significantly down-regulated expression of genes and proteins of multiple key components in the Ras/Rho GTPases molecular switch, including Ran, Rab, Rac, Rap, and Ral, was observed on gene and protein expression profiles and further validated by Western blot analysis. Ectopic activation of FHIT in FHIT-deficient H1299 cells also significantly reduced the invasive potential of tumor cells by down-regulating expression of RhoC, a potential marker of tumor cell invasion and metastases. A simultaneous knockdown of the expression of several key Ras/Rho signaling molecules using gene-specific small interfering RNAs (RHO-siRNA) targeting selected Rab11, Rac1, and Rap1 genes significantly inhibited tumor cell growth and induced apoptosis in NSCLC cells in vitro, and a local injection of RHO-siRNAs complexed with N-[1-(2,3-dioleoyloxyl)propyl]-N,N,N-trimethylammoniummethyl sulfate:cholesterol nanoparticles inhibited tumor growth in A549 tumor xenografts in mice, mimicking the AdFHIT-mediated tumor-suppressing effect. These results suggest a new role of FHIT in down-regulating the Ras/Rho GTPase-associated oncogenic signaling pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10379-88
pubmed:meshHeading
pubmed-meshheading:17974981-Acid Anhydride Hydrolases, pubmed-meshheading:17974981-Animals, pubmed-meshheading:17974981-Apoptosis, pubmed-meshheading:17974981-Blotting, Western, pubmed-meshheading:17974981-Carcinoma, Non-Small-Cell Lung, pubmed-meshheading:17974981-Cell Line, Tumor, pubmed-meshheading:17974981-Female, pubmed-meshheading:17974981-Genes, ras, pubmed-meshheading:17974981-Humans, pubmed-meshheading:17974981-Lung Neoplasms, pubmed-meshheading:17974981-Mice, pubmed-meshheading:17974981-Neoplasm Invasiveness, pubmed-meshheading:17974981-Neoplasm Proteins, pubmed-meshheading:17974981-Protein Array Analysis, pubmed-meshheading:17974981-RNA, Small Interfering, pubmed-meshheading:17974981-Signal Transduction, pubmed-meshheading:17974981-Tumor Suppressor Proteins, pubmed-meshheading:17974981-rho GTP-Binding Proteins
pubmed:year
2007
pubmed:articleTitle
Fragile histidine triad-mediated tumor suppression of lung cancer by targeting multiple components of the Ras/Rho GTPase molecular switch.
pubmed:affiliation
Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, 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