Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
1996-9-24
pubmed:abstractText
Anti-IgM treatment of Burkitt's lymphoma cells is followed by either growth arrest or induction of apoptosis. In this study we have explored the role of c-myc in these events. Our results in Ramos cells indicate the following. (a) The decline in c-myc mRNA occurs at about 4 h; inhibition of about 80% being observed. (b) The stability of c-myc message is involved since the half-life of c-myc mRNA is decreased from about 30 min in untreated cells to about 15 min following treatment with anti-IgM. In the presence of cycloheximide, a protein synthesis inhibitor, the half-life is increased to about 50 min and was unaltered by treatment with anti-IgM. (c) By contrast, nuclear run-on experiments indicated no change in transcription rates for c-myc message due to treatment with anti-IgM. (d) A decrease in c-myc causes apoptosis since specific repression of c-myc with antisense oligonucleotides decreases the levels of c-Myc, inhibits growth rate, decreases viability, and induces apoptosis. (e) Anti-CD40 inhibition of apoptosis occurs without alteration in anti-IgM-induced down-regulation of c-myc mRNA, suggesting that it acts distally to c-myc down-regulation. Other cell lines were also investigated. In Epstein-Barr virus (EBV)-positive cell lines (Daudi, Raji, and Namalwa), anti-IgM treatment for 24 h results in growth inhibition without induction of apoptosis. In EBV-negative cell lines (ST486 and CA46, as well as Ramos), a more heterogeneous pattern of responses to anti-IgM are observed. Ramos and ST486 cells both show growth inhibition and apoptosis upon anti-IgM treatment; CA46 cells shown only growth inhibition but not apoptosis. Anti-IgM causes a decline in c-myc mRNA levels in all of these lines, as well as in c-Myc protein level in the two lines investigated, Daudi and Ramos, regardless of apoptosis. Addition of antisense c-myc oligonucleotides to the cells reduced growth in both Daudi and Ramos cells lines, however it resulted in substantial apoptosis only in Ramos cells. These results suggest that anti-IgM destabilizes c-myc mRNA by a process that involves mRNA turnover, rather than transcription rates. However anti-IgM exerts differential effects in EBV-positive and EBV-negative cell lines. EBV-positive cells are uniformly resistant to apoptosis, while EBV-negative cell lines show a tendency to apoptosis but with exceptions. Growth inhibition can be uncoupled from apoptosis in EBV-positive cell lines, but not in those EBV-negative cell lines prone to apoptosis. Furthermore, down-regulation of c-myc message correlates with growth inhibition in these cells, but is an insufficient link to apoptosis. By contrast inhibition of apoptosis by anti-CD40 occurs even though c-myc mRNA is decreased.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
271
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18875-84
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8702548-Antibodies, Anti-Idiotypic, pubmed-meshheading:8702548-Antigens, CD40, pubmed-meshheading:8702548-Apoptosis, pubmed-meshheading:8702548-Base Sequence, pubmed-meshheading:8702548-Burkitt Lymphoma, pubmed-meshheading:8702548-Cell Division, pubmed-meshheading:8702548-Cell Line, pubmed-meshheading:8702548-Genes, myc, pubmed-meshheading:8702548-Herpesvirus 4, Human, pubmed-meshheading:8702548-Humans, pubmed-meshheading:8702548-Immunoglobulin M, pubmed-meshheading:8702548-Molecular Sequence Data, pubmed-meshheading:8702548-Oligonucleotides, Antisense, pubmed-meshheading:8702548-Proto-Oncogene Proteins c-myc, pubmed-meshheading:8702548-RNA, Messenger, pubmed-meshheading:8702548-RNA, Neoplasm, pubmed-meshheading:8702548-Tumor Cells, Cultured, pubmed-meshheading:8702548-Viral Proteins
pubmed:year
1996
pubmed:articleTitle
Anti-IgM-mediated regulation of c-myc and its possible relationship to apoptosis.
pubmed:affiliation
Regional Research Laboratory, Kaiser Foundation Hospitals, Los Angeles, California 90027, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't