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Changes in frequency, morphology, and behavior of tumors induced in mice by a polyoma virus mutant with a
R Freund1, C J Dawe, J P Carroll
1Department of Pathology, Harvard Medical School, Boston, MA 02115.
Abstract:
Alterations in the tumor-inducing ability of a polyoma virus mutant encoding a partially defective middle T oncogene have been investigated. The mutant middle T associates with and activates the tyrosine protein kinase pp60c-src normally but does not promote binding of a second enzyme, phosphatidyl-inositol 3-kinase. Compared with the wild type virus, this mutant shows an altered and reduced ability to induce tumors after inoculation into newborn mice, as judged by the following criteria: lower frequency of tumors, reduced morbidity and increased survival times of host mice, changes in the spectrum of tumor types, and altered morphologic properties of tumors at several target organ sites. These results indicate an important role of changes in 3-phosphoinositide metabolism in induction of a variety of tumors in this experimental system.
Insights
A polyoma virus mutant with a defective middle T oncogene showed reduced tumor formation in mice. This highlights the role of phosphatidyl-inositol 3-kinase in tumor development.
Area of Science:
- Virology
- Oncology
- Molecular Biology
Background:
- Polyoma virus middle T oncogene is crucial for tumor induction.
- Middle T oncogene's interaction with cellular kinases is key to its function.
Purpose of the Study:
- Investigate the impact of a defective middle T oncogene on tumor induction.
- Determine the role of phosphatidyl-inositol 3-kinase in polyoma virus-induced tumorigenesis.
Main Methods:
- Generated a polyoma virus mutant with a partially defective middle T oncogene.
- Assessed tumor induction in newborn mice inoculated with the mutant virus.
- Analyzed protein kinase and phosphoinositide binding activities of the mutant middle T.
Main Results:
- The mutant middle T associated with pp60c-src but failed to bind phosphatidyl-inositol 3-kinase.
- Mutant virus exhibited reduced tumor frequency, lower morbidity, and increased host survival.
- Observed altered tumor spectrum and morphology in mice infected with the mutant virus.
Conclusions:
- Phosphatidyl-inositol 3-kinase binding is essential for middle T oncogene-mediated tumor induction.
- Alterations in 3-phosphoinositide metabolism significantly impact polyoma virus-induced tumorigenesis.
- Middle T oncogene's interaction with phosphatidyl-inositol 3-kinase is critical for diverse tumor development.