INCREASED EXPRESSION OF SCHWANNOMA-DERIVED GROWTH-FACTOR (SDGF) MESSENGER-RNA IN RAT-TUMOR CELLS - INVOLVEMENT OF SDGF IN THE GROWTH PROMOTION OF RAT GLIOMAS

Schwannoma-derived growth factor (SDGF) is a member of the epidermal g rowth factor (EGF) family, having mitogenic activity on rat astrocytes , fibroblasts and Schwann cells. The SDGF gene is significantly expres sed in the newborn rat lung and in the adult rat sciatic nerve. Howeve r, except for one rat schwannoma cell line, from which SDGF and its cD NA were isolated, nothing is known about SDGF expression in establishe d tumor cell lines. We examined the expression level of the SDGF gene in a variety of rat tumor cell lines by Northern blotting and found th at it was increased in 11 of 25 established lines. The most abundant S DGF mRNA, which was about 50-fold higher than in the newborn rat lung, was expressed in rat liver adenoma dRLa74 cells. In rat glioma cell l ines, such as C6, 9L and T9, and in the rat hepatoma dRLh84 and H411E cells, the SDGF expression level was about in-fold higher than in the newborn rat lung. In 8 of 13 cell lines expressing SDGF mRNA, the EGF receptor (EGFR) gene, the product of which is regarded as a functional receptor of SDGF, was co-expressed, In addition, transfected gene-dep endent anti-sense SDGF RNA expression under the control of the human m etallothionein promoter significantly suppressed the in vitro growth a s well as in vivo tumorigenicity of 9L glioma cells. Our results sugge st that SDGF acts as an autocrine growth factor in the development and growth of rat tumors such as gliomas. (C) 1996 Wiley-Liss, Inc.