INDUCIBLE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN IN HT-1080 HUMAN FIBROSARCOMA CALLS

Glial fibrillary acidic protein (GFAP) is an intermediate filament pro tein expressed almost exclusively by glial cells of the central nervou s system. We have previously transfected GFAP-negative human astrocyto ma cells with the gene for GFAP and have demonstrated that GFAP transf ection decreases astrocytoma proliferation and alters astrocytoma morp hology. To determine if the same cellular responses could be elicited upon GFAP transfection of nonglial tumor cells, in the present study w e have transfected a GFAP-negative human malignant fibrosarcoma cell l ine (HT-1080) with a cDNA containing the entire coding sequence of the human GFAP gene under the control of an inducible metallothionein pro moter, Stably transfected HT-1080 clones were identified that are GFAP -positive by PCR and immunocytochemistry. GFAP-positive HT-1080 fibros arcoma cells also demonstrate a decrease in tumor cell proliferation, altered morphological features characterized by cell elongation and cy toplasmic process formation, and reduction of invasive potential when compared to controls. These findings suggest that the inducible expres sion of the cytoskeletal protein GFAP can also be associated with dram atic cellular effects in nonglial non-central nervous system tumor cel ls.