Fibroblast Growth Factor Inhibits Proliferation of a Highly Tumorigenic Insulin-Independent Teratoma-Derived Cell Line

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Abstract
The present paper examines the effect of basic fibroblast growth factor (bFGF) on the proliferation of teratoma-derived cell lines having increased tumorigenic properties isolated from the non-tumorigenic adipogenic cell line 1246. Although FGF is a mitogen for the non tumorigenic 1246 cells and for the moderately tumorigenic 1246-3A cells derived from the 1246 cells, bFGF inhibits the proliferation and DNA synthesis of the highly tumorigenic PC cells starting at concentration as low as 30 pg/ml. The inhibitory effect of FGF on PC cell growth is irreversible as demonstrated by the inability of the cells to resume proliferation once FGF is removed from the culture medium. Comparison of l25I-bFGF binding to the three cell lines was performed. Based on the Scatchard analysis of the binding data, PC cells display only low affinity class of FGF binding sites whereas 1246 and 1246-3A cells presented also high affinity binding sites. The inhibitory effect of FGF on PC cells did not go through activation of a PKC mediated pathway, which is also known to inhibit PC cell proliferation, since FGF inhibition of PC cell growth was still apparent after PKC down regulation. FGF was still able to transiently stimulate the expression of mRNA for early growth associated genes as demonstrated by c-myc and c-fos expression, although it inhibited cell proliferation on PC cells. Our data demonstrate that the highly tumorigenic teratoma cells acquire an inhibitory response for a factor which is growth stimulatory to non-tumorigenic and moderately tumorigenic cells from which they are derived.