Cell Growth & Differentiation, Vol 7, Issue 12 1697-1703, Copyright © 1996 by American Association of Cancer Research
Inducible expression of glial fibrillary acidic protein in HT-1080 human fibrosarcoma cells
M Murakami, K Fukuyama, S Hubbard, K Matsuzawa, PB Dirks and JT Rutka
Brain Tumor Research Laboratory, Hospital for Sick Children, University of Toronto, Ontario, Canada.
Glial fibrillary acidic protein (GFAP) is an intermediate filament protein
expressed almost exclusively by glial cells of the central nervous system.
We have previously transfected GFAP-negative human astrocytoma cells with
the gene for GFAP and have demonstrated that GFAP transfection decreases
astrocytoma proliferation and alters astrocytoma morphology. To determine
if the same cellular responses could be elicited upon GFAP transfection of
nonglial tumor cells, in the present study we have transfected a
GFAP-negative human malignant fibrosarcoma cell line (HT-1080) with a cDNA
containing the entire coding sequence of the human GFAP gene under the
control of an inducible metallothionein promoter. Stably transfected
HT-1080 clones were identified that are GFAP-positive by PCR and
immunocytochemistry. GFAP-positive HT-1080 fibrosarcoma cells also
demonstrate a decrease in tumor cell proliferation, altered morphological
features characterized by cell elongation and cytoplasmic process
formation, and reduction of invasive potential when compared to controls.
These findings suggest that the inducible expression of the cytoskeletal
protein GFAP can also be associated with dramatic cellular effects in
nonglial non-central nervous system tumor cells.