The GR-FeSV onc gene, v-fgr, appears to contain genes coding for actin as well as a tyrosine-specific protein kinase. In an effort to understand the role of the actin domain in the transforming ability of the virus, a series of mutants with deletions in their gag and/or actin sequences were constructed and tested for their ability to transform NIH/3T3 cells. Preliminary data suggest that the actin domain has little effect on transforming activity in vitro but that the carboxy terminus of the gag sequences might be important for membrane binding and transformation. Expression of the human fgr proto-oncogene is limited to Burkitt's lymphomas naturally infected with Epstein-Barr virus (EBV) but not to EBV-negative Burkitt's lymphoma. Normal umbilical cord or peripheral blood lymphocyte lines established in vitro by EBV infection also contain detectable c-fgr mRNA. A 50-fold increase in steady state mRNA concentration is observed when uninfected Burkitt's lymphoma cell lines are deliberately infected with EBV. These findings demonstrate, for the first time, the induction of a proto-oncogene in response to infection by a DNA tumor virus. Effects to identify normal sources of fgr proto-oncogene expression have revealed that high levels of c-fgr mRNA are detected in monocytes as well as resting polymorphonuclear leukocytes (PMNs). Although high levels of c-fgr mRNA are present in resting PMNs, the fgr proto-oncogene is transcriptionally inactive, implying that it is synthesized at an earlier stage of granulocytic maturation and is found in the mature PMN as a stable mRNA species. These findings suggest an important role for the fgr proto-oncogene in some facet of granulocytic maturation or function.

Agency
National Institute of Health (NIH)
Institute
Division of Cancer Epidemiology And Genetics (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005456-04
Application #
3939709
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code