Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice

Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice

Eric C. Holland* and
Harold E. Varmus

Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

Contributed by Harold E. Varmus

Abstract

Basic fibroblast growth factor (bFGF) is overexpressed in most high-grade human gliomas, implying that it is involved in the pathogenesis of these tumors. To assess the biological effect of inappropriate production of bFGF in normal astrocytes, we developed a system for glia-specific gene transfer in transgenic mice. A transgene encoding the receptor for subgroup A avian leukosis virus and controlled by the astrocyte-specific glial fibrillary acidic protein promoter permits efficient glia-specific transfer of genes carried by subgroup A avian leukosis virus vectors. With this system, we have demonstrated that bFGF induces proliferation and migration of glial cells in vivo, without the induction of tumors.

Footnotes

↵ * To whom reprint requests should be addressed at: Division of Basic Sciences, National Cancer Institute, National Institutes of Health, 49 Convent Drive, Building 49, Room 4A56, Bethesda, MD 20892. e-mail: eholland{at}nhgri.nih.gov.
↵ † The rabbit polyclonal antibody was produced by John Young (Harvard University) and Paul Bates (University of Pennsylvania).
ABBREVIATIONS:

RCAS,

replication-competent ALV;

AP,

alkaline phosphatase;

bFGF,

basic fibroblast growth factor;

GFAP,

glial fibrillary acidic protein;

ALV,

avian leukosis virus;

TVA,

receptor for ALV-A;

CEF,

chicken embryo fibroblast;

MLV,

murine leukemia virus