Oncogene involvement in radiation- and virus-induced mouse osteosarcomas

Area of Science:

• Oncology
• Virology
• Molecular Biology

Background:

• Internal irradiation with bone-seeking radionuclides induces bone tumors in mice.
• Endogenous retroviruses are activated during tumor development.
• Osteosarcoma cell lines provide a model for studying radiation-induced bone cancers.

Purpose of the Study:

• To investigate the role of retroviral integration in 90Sr-induced bone tumors.
• To characterize the FBR-MuSV transforming retrovirus and its oncogenic potential.
• To analyze the genetic alterations associated with radiation-induced bone cancer.

Main Methods:

• Genomic DNA cotransfection and G418 selection.
• Southern blot analysis of proviral sequences and cellular junction fragments.
• Primary structure determination of FBR-MuSV and analysis of fos-containing mRNAs.

Main Results:

• Cotransfection of osteosarcoma DNA into NIH/3T3 cells resulted in transformation and revealed extra copies of c-ras.
• Rearrangements of 3' provirus cellular junction fragments were observed in all analyzed tumor DNAs, without site-specific integration.
• FBR-MuSV was characterized, containing altered murine c-fos sequences and inducing specific fos-containing mRNAs in transformed cells.

Conclusions:

• Retroviral integration and rearrangements are implicated in the development of radiation-induced bone tumors.
• The FBR-MuSV retrovirus, with its modified c-fos oncogene, is a potent inducer of bone tumors.
• Understanding these mechanisms provides insights into oncogenesis and potential therapeutic targets.