Search for Common Sites of Proviral Integrations of MAV-2 Retrovirus

Tumour types

nephroblastoma, lung angiosarcoma, liver angiosarcoma, hepatocellular carcinoma, cholangiocarcinoma, tissue cultures in vitro

Acknowledgements

Created with support of the Czech Science Foundation – Grant No. GA301/09/1727

Multifarious aspects of cell transformation revealed in the model of insertional mutagenesis by MAV-2

Oncogenic retroviruses contribute to malignant transformation of cells in two possible ways – through direct transduction of an oncogenically activated gene (acute oncogenic retroviruses) or through insertional mutagenesis (non-acute oncogenic retroviruses). Myeloblastosis-associated virus 2 (MAV-2) is a chicken oncogenic retrovirus with the unique ability to induce development of various types of experimental tumors including nephroblastoma (tumor of embryonic origin), angiosarcoma of lungs, liver and heart, liver carcinoma, cholangiocarcinoma and other rare tumor types. Genes found to be recurrently hit by clonal insertion of the MAV-2 provirus in independent clonal tumors are thought to be cancer genes and their deregulation/mutation is responsible for transformation of the host cell.

We used a chicken MAV-2-based model of insertional mutagenesis to identify the genes whose deregulation is responsible for the formation of chicken nephroblastoma (Pecenka et. al., 1988 and 2011, Pajer et. al. 2003 and 2006), lung angiosarcoma (Pajer et. al. 2009), liver angiosarcoma, hepatocarcinoma and cholangiocarcinoma (submitted) and for transformation in vitro (in prep.). Detailed study of the cooperation of MAV-2 insertional mutagenesis and promotional effects of stray cells in lung sarcoma induction lead us to the formulation of the industasis concept (Pajer et. al. 2009). Thus, the single experimental tool, MAV-2 retrovirus, affords the opportunity to study and compare the molecular mechanisms underlying the formation of tumors of different origin and histology as well as contribution of nongenetic factors to tumor formation. Our current effort is concentrated on identification of the positions of clonally integrated proviruses in the host genome and analysis of deregulation of the adjacent host genes. The data obtained also allow cross-species comparison of the mechanisms of cell transformation – a necessary step in the effort to understand the complex problem of tumorigenesis.

Results

Table of Proviral Integration Sites

Contact and Feedback

Petr Pajer - petr.pajer@img.cas.cz

References

Pecenka V, Karafiat V, Kasparova P, Dudlova J, Dvorak M, Pajer P. Distinct Cancer Genes Initiate Different Liver Tumor Types in a New Retrovirus-based Chicken Model of Cancerogenesis. (submitted)

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Pajer P, Karafiat V, Pecenka V, Prukova D, Dudlova J, Plachy J, Kasparova P, Dvorak M. Industasis, a promotion of tumor formation by nontumorigenic stray cells. Cancer Res 69(11): 4605-12, 2009. [Pubmed] [DOI]

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