Linked Life Data

11313935

Source:http://linkedlifedata.com/resource/pubmed/id/11313935

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2001-4-23
pubmed:abstractText
It is well accepted that the Bcr-Abl oncoprotein encoded by the Philadelphia chromosome is responsible for causing chronic myelogenous leukemia (CML). We have previously demonstrated that expression of Bcr interferes with the oncogenic effects of Bcr-Abl. To examine the effects of increased Bcr expression on Bcr-Abl oncogenic effects in a more physiological system, we tested the leukemogenic potential of a clone of K562 cells (K6 K562) containing an inducible BCR gene in NOD/scid mice. In this clone, the BCR gene was placed under the control of a tetracycline (Tet) repression system with a cytomegalovirus (CMV) promoter. Induction of exogenous Bcr protein by removal of Tet from the culture medium caused a dramatic increase in Bcr serine kinase activity, yielding predominantly phosphoserine Bcr, despite the presence of Bcr-Abl in the kinase reaction mixture. Prior to induction, the endogenous Bcr was predominantly in the phosphotyrosine form because of phosphorylation by Bcr-Abl, which we previously have shown suppresses Bcr serine/threonine kinase activity. Injection of K6 K562 cells into NOD/scid mice under conditions where BCR expression was suppressed resulted in death or terminal illness in 100% of the mice within 35 days after injection. These mice had a severe wasting syndrome characterized by atrophy of bone marrow hematopoiesis, and/or neoplasia of liver, bone marrow and spleen. Neoplastic spleens from these mice usually contained b3a2 Bcr-Abl transcripts. In contrast, induction of BCR expression at the time of injection allowed 80% survival; these healthy mice had no detectable microscopic lesions in blood forming organs. This difference in survival was significant with P<0.0001. Of interest, mice that were fed Tet for 19 days to initiate the disease syndrome and then released from the BCR transcriptional block had a significantly better survival pattern than mice exposed to Tet throughout the entire period. Moreover, 30% of these mice (three mice) survived through day 50. We conclude from these findings that BCR gene expression strongly inhibits the oncogenic effects of Bcr-Abl in NOD/scid mice, yielding healthy mice in most cases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0950-9232
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1873-81
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11313935-Animals, pubmed-meshheading:11313935-Fusion Proteins, bcr-abl, pubmed-meshheading:11313935-Gene Expression Regulation, pubmed-meshheading:11313935-Humans, pubmed-meshheading:11313935-K562 Cells, pubmed-meshheading:11313935-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:11313935-Mice, pubmed-meshheading:11313935-Mice, Inbred NOD, pubmed-meshheading:11313935-Mice, SCID, pubmed-meshheading:11313935-Oncogene Proteins, pubmed-meshheading:11313935-Oncogenes, pubmed-meshheading:11313935-Phosphorylation, pubmed-meshheading:11313935-Protein-Tyrosine Kinases, pubmed-meshheading:11313935-Proto-Oncogene Proteins, pubmed-meshheading:11313935-Proto-Oncogene Proteins c-bcr, pubmed-meshheading:11313935-RNA, Messenger, pubmed-meshheading:11313935-Serine, pubmed-meshheading:11313935-Tyrosine
pubmed:year
2001
pubmed:articleTitle
BCR gene expression blocks Bcr-Abl induced pathogenicity in a mouse model.
pubmed:affiliation
Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, TX 77030, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.