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American Journal of Pathology, Vol 141, 1409-1425, Copyright © 1992 by American Society for Investigative Pathology

REGULAR ARTICLES

Changes in frequency, morphology, and behavior of tumors induced in mice by a polyoma virus mutant with a specifically altered oncogene

R Freund, CJ Dawe, JP Carroll and TL Benjamin
Department of Pathology, Harvard Medical School, Boston, MA 02115.

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.

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