Linked Life Data

10648380

Source:http://linkedlifedata.com/resource/pubmed/id/10648380

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-2-24
pubmed:abstractText
One major obstacle to the effective treatment of cancer is to distinguish between tumor cells and normal cells. The chimeric molecules created by cancer-associated chromosomal abnormalities are ideal therapeutic targets because they are unique to the disease. We describe the use of a novel approach based on the catalytic RNA subunit of RNase P to destroy specifically the tumor-specific fusion genes created as a result of chromosome abnormalities. Using as a target model the abnormal BCR-ABL p190 and p210 products, we constructed M1-RNA with guide sequences that recognized the oncogenic messengers at the fusion point (M1-p190-GS and M1-p210-GS). To test the effectiveness and the specificity of M1-p190-GS and M1-p210-GS, we studied in vitro and in vivo effects of these RNA enzymes against BCR-ABL(p190) and BCR-ABL(p210), bearing in mind that both fusion genes share the ABL sequence but differ in the sequence coming from the BCR gene. We showed that M1-p190-GS and M1-p210-GS can act as sequence-specific endonucleases and can exclusively cleave target RNA that forms a base pair with the guide sequence (GS). We also demonstrated that when M1-p190-GS and M1-p210-GS were expressed in proper mammalian cell models, they abolished the effect of BCR-ABL by specifically decreasing the amount of the target BCR-ABL mRNA and preventing the function of the BCR-ABL oncogenes. These data clearly demonstrate the usefulness of the catalytic activity of M1-GS RNA to cleave specifically the chimeric molecules created by chromosomal abnormalities in human cancer and to represent a novel approach to cancer treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
731-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10648380-Animals, pubmed-meshheading:10648380-Antineoplastic Agents, pubmed-meshheading:10648380-Base Sequence, pubmed-meshheading:10648380-Drug Design, pubmed-meshheading:10648380-Endoribonucleases, pubmed-meshheading:10648380-Fusion Proteins, bcr-abl, pubmed-meshheading:10648380-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10648380-Genes, abl, pubmed-meshheading:10648380-Humans, pubmed-meshheading:10648380-Mice, pubmed-meshheading:10648380-Molecular Sequence Data, pubmed-meshheading:10648380-Neoplasms, pubmed-meshheading:10648380-Oncogenes, pubmed-meshheading:10648380-RNA, Catalytic, pubmed-meshheading:10648380-RNA, Messenger, pubmed-meshheading:10648380-RNA, Neoplasm, pubmed-meshheading:10648380-Ribonuclease P, pubmed-meshheading:10648380-Substrate Specificity, pubmed-meshheading:10648380-Transfection, pubmed-meshheading:10648380-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
In vivo inhibition by a site-specific catalytic RNA subunit of RNase P designed against the BCR-ABL oncogenic products: a novel approach for cancer treatment.
pubmed:affiliation
Department of Cell Growth and Differentiation, Institute of Microbiology and Biochemistry, CSIC/University of Salamanca, Salamanca, Spain.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't