Linked Life Data

12878165

Source:http://linkedlifedata.com/resource/pubmed/id/12878165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-7-24
pubmed:abstractText
Activity of the independently regulated human c-myc P0 promoter has been associated with the undifferentiated status of leukemia cells as well as the hormone-independent proliferation of breast cancer cells. The P0 transcript is distinguished from the predominant P1 and P2 c-myc mRNAs by an approximately 639-nucleotide extension of the 5'-untranslated region. We hypothesized that this complex 5'-untranslated RNA sequence unique to the P0 transcript may contribute significantly to the composite regulation of the c-myc locus and that enforced intracellular synthesis of the isolated P0 5'-UTR, out of its native sequence context, might amplify or dominantly interfere with its normal regulatory function. Human tumor (HeLa) cells in which the isolated P0 5'-UTR was ectopically expressed displayed a dramatic decrease in anchorage-independent proliferation. Furthermore, P0 5'-UTR-expressing HeLa cells failed to form tumors when inoculated into SCID mice. This loss of tumorigenicity was associated with increases in levels of the c-Myc1 (p67) and c-Myc2 (p64) proteins and a 3- to 5-fold elevation of spontaneous apoptotic index. These results demonstrate that an isolated 5'-untranslated RNA sequence can be attributed potent in trans gene-regulatory and phenotype-altering capabilities and that extrinsic alterations in c-myc regulation can be utilized to reestablish the natural proapoptotic (tumor suppressor) activities associated with this protooncogene.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-4827
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
131-42
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Inhibition of tumorigenicity by the 5'-untranslated RNA of the human c-myc P0 transcript.
pubmed:affiliation
Department of Medicine, University of Alabama at Birmingham, Tumor Institute, Room 508, 1824 6th Avenue South, Birmingham, AL 35294-3300, USA. scott.blume@ccc.uab.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't