Related Experiment Videos
Svi3: A provirus common integration site in c-myc in SL/Kh pre-B lymphomas
Guang Jin1, Tatsuaki Tsuruyama, Yoshihiro Yamada
1Department of Pathology and Biology of Diseases, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract:
Spontaneous pre-B lymphomas in SL/Kh mice occur by somatic acquisition of a provirus genome of endogenous murine leukemia virus (MuLV). Inverse PCR amplification and sequence analyses of a provirus and its host flanking fragment revealed a proviral insertion into c-myc in 3 out of 60 SL/Kh pre-B lymphomas, named Svi3 lymphomas (SL/Kh virus integration site-3). Southern blot analysis revealed that two lymphomas had clonal integration in c-myc exon 1 and the other, in the promoter region. In 2 out of 3 Svi3 lymphomas, a fusion transcript of provirus 3' long terminal repeat and c-myc and a normal full-length c-myc transcript were obtained, but in one Svi3 lymphoma, only the normal transcript was obtained. All three Svi3 lymphomas had increased c-myc expression, producing normal 67-kDa c-Myc protein. Svi3 lymphomas had more mature phenotypes in the steps of early B-cell differentiation than Svi1 lymphomas, in which c-myc expression was indirectly up-regulated by provirus integration into Stat5a.
Insights
Spontaneous lymphomas in SL/Kh mice arise from murine leukemia virus (MuLV) proviral insertions. Three lymphomas showed c-myc gene integration, leading to increased c-myc expression and altered B-cell differentiation.
Area of Science:
- Oncology
- Virology
- Immunology
Background:
- Spontaneous pre-B cell lymphomas in SL/Kh mice are linked to endogenous murine leukemia virus (MuLV) proviral genome acquisition.
- Understanding the precise mechanisms of oncogene activation in lymphomagenesis is crucial for therapeutic development.
Purpose of the Study:
- To investigate the role of MuLV proviral integration in the c-myc oncogene in SL/Kh mouse lymphomas.
- To characterize the molecular events and phenotypic consequences of c-myc dysregulation in these lymphomas.
Main Methods:
- Inverse PCR amplification and sequence analysis to identify proviral integration sites.
- Southern blot analysis to confirm clonal integration.
- Analysis of c-myc transcript levels and protein expression.
Main Results:
- Proviral insertion into the c-myc gene was identified in 3 out of 60 SL/Kh pre-B lymphomas (Svi3 lymphomas).
- Integration occurred in c-myc exon 1 or the promoter region, leading to increased c-myc expression and normal 67-kDa c-Myc protein production.
- Svi3 lymphomas exhibited more mature B-cell phenotypes compared to lymphomas with Stat5a integration.
Conclusions:
- Somatic acquisition of MuLV proviruses can directly activate the c-myc oncogene through integration.
- Direct c-myc activation by proviral insertion contributes to lymphomagenesis and influences B-cell differentiation.
- These findings highlight distinct pathways of oncogene activation in MuLV-induced lymphomas.