Rapid Induction of IgM-Secreting Murine Plasmacytomas by Pristane and an Immunoglobulin Heavy-Chain Promoter/Enhancer-Driven c-myc/v-Ha-ras Retrovirus

A retroviral vector, RIM, containing murine c-myc under the control of immunoglobulin heavy-chain gene promoter and enhancer elements and v-Ha-ras driven by a Moloney murine leukemia virus long terminal repeat induced IgM-secreting plasmacytomas in 28% of adult and 83% of 3-week-old pristane-conditi...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 85; no. 16; pp. 6067 - 6071
Main Authors Clynes, Raphael, Wax, Judy, Stanton, Lawrence W., Smith-Gill, Sandra, Potter, Michael, Marcu, Kenneth B.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 01.08.1988
National Acad Sciences
Subjects
Animals
B lymphocytes
DNA probes
Enhancer Elements, Genetic
Genes, Immunoglobulin
Immunoglobulin Heavy Chains - metabolism
Immunoglobulin M - metabolism
Immunoglobulins
Mice
Mice, Inbred BALB C
Mice, Inbred DBA
myc genes
Plasmacytoma
Plasmacytoma - etiology
Plasmacytoma - immunology
Promoter Regions, Genetic
Proto-Oncogenes
Proviruses
Recombination, Genetic
Retroviridae
Retroviridae - genetics
Terpenes - pharmacology
Tumors
Viruses
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Summary:A retroviral vector, RIM, containing murine c-myc under the control of immunoglobulin heavy-chain gene promoter and enhancer elements and v-Ha-ras driven by a Moloney murine leukemia virus long terminal repeat induced IgM-secreting plasmacytomas in 28% of adult and 83% of 3-week-old pristane-conditioned mice with mean latency periods of 60-70 days. In contrast, the same vector only harboring c-myc or v-Ha-ras was virtually ineffective. RIM-induced plasmacytomas expressed retroviral myc and ras genes while their endogenous c-myc alleles were unrearranged and transcriptionally inactive. These plasmacytomas were clonal as each possessed a unique immunoglobulin heavy-chain joining region rearrangement and a single recombinant provirus. Moloney murine leukemia helper virus did not play an obligatory role in tumorigenesis since insertions of Moloney murine leukemia proviruses were found in only 6 of 24 plasmacytomas induced in adult mice. Taken together, these findings support the view that the v-Ha-ras oncogene can cooperate with an activated myc gene in pristane plasmacytomagenesis.
Bibliography:ObjectType-Article-2
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ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.16.6067