Mouse mammary tumor proviruses from a T-cell lymphoma are associated with the retroposon L1Md
1Department of Microbiology, University of Texas, Austin 78712-1095.
Abstract:
Four Charon 4A clones containing mouse mammary tumor virus (MMTV) proviruses and their cellular flanking sequences were obtained from partial EcoRI libraries of a C57BL/6 T-cell lymphoma with both endogenous and newly acquired MMTV proviruses. The cellular flanking sequences of three of four MMTV proviruses contained DNA homologous to the 3' end of the long interspersed retroposon L1Md. Two of the three proviruses were newly acquired in the lymphoma DNA, and these MMTV proviruses appeared to be 5 kilobases downstream and in the same transcriptional orientation as the L1 sequence. The third provirus was endogenous Mtv-9 and was located less than 500 base pairs from the 3' end of L1. Seven additional clones containing MMTV proviruses were isolated from partial MboI libraries of a B6 T-cell lymphoma. Five of the seven clones contained L1 elements in the cellular DNA flanking MMTV DNA. At least two clones (including one with the Mtv-8 provirus) had multiple L1 copies flanking the MMTV provirus, and one clone contained a single MMTV long terminal repeat directly integrated into a truncated L1 sequence. Although the frequencies of B1 and L1 in random library clones were similar, only one MMTV-containing clone hybridized to the abundant repetitive element B1. These data suggest a nonrandom association between MMTV and L1Md.
Insights
Mouse mammary tumor virus (MMTV) proviruses show a nonrandom association with the long interspersed retroposon L1Md in T-cell lymphoma DNA. This suggests a potential link between MMTV integration and L1 elements in cancer development.
Area of Science:
- Molecular Biology
- Virology
- Genomics
Background:
- Mouse mammary tumor virus (MMTV) is a retrovirus implicated in mammary tumorigenesis.
- Long interspersed retroposon L1Md elements are mobile DNA sequences found in mammalian genomes.
- The integration patterns of MMTV proviruses in host DNA can influence viral gene expression and oncogenesis.
Purpose of the Study:
- To investigate the association between MMTV proviruses and repetitive DNA elements in T-cell lymphoma.
- To determine if MMTV integration occurs randomly or shows preference for specific genomic regions, particularly those containing L1 elements.
Main Methods:
- Construction and screening of partial EcoRI and MboI genomic libraries from C57BL/6 T-cell lymphoma.
- Isolation and characterization of Charon 4A clones containing MMTV proviruses and flanking cellular DNA.
- Hybridization studies using probes for MMTV, L1Md, and B1 repetitive elements.
Main Results:
- Four of four MMTV-containing clones from EcoRI libraries showed flanking sequences homologous to the 3' end of L1Md.
- Two newly acquired MMTV proviruses were located downstream of L1 sequences, while an endogenous Mtv-9 provirus was closely associated with L1.
- Five of seven MMTV-containing clones from MboI libraries also contained L1 elements, with some showing multiple L1 copies or MMTV LTR integration into L1.
Conclusions:
- The data strongly suggest a nonrandom association between MMTV proviruses and L1Md elements in T-cell lymphoma.
- This nonrandom integration pattern may indicate a role for L1 elements in MMTV integration or vice versa.
- Further research is warranted to elucidate the mechanisms driving this observed association and its implications for MMTV-induced lymphomagenesis.
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