FIBROBLAST GROWTH-FACTOR-RECEPTOR-1 AND GROWTH-FACTOR-RECEPTOR-2 ARE DIFFERENTIALLY REGULATED IN MURINE EMBRYONAL CARCINOMA-CELLS AND IN RESPONSE TO FIBROBLAST GROWTH-FACTOR-IV

We have studied the expression of two of the receptors for fibroblast growth factors, FGFR-1 and FCFR-2, in response to ligand binding and i n embryonal carcinoma (EC cells). Exposure of mouse fibroblasts to FGF -4 or FGF-2 results in a drastic downregulation of the mRNA levels for FGFR-2, while expression of FCFR-1 mRNA appears unaffected. Furthermo re, FCF-4 transformed cells display low levels of FCFR-2 mRNA and thes e levels are significantly increased by treatment with anti FGF-4 neut ralizing antibodies. In undifferentiated F9 EC cells, the levels of FG FR-2 mRNA are very low and increase substantially upon induction of di fferentiation. The levels of mRNA for FGFR-1 are again unaffected. To gain information on the regulation of expression of the gene encoding FGFR-2 (bek) we have cloned the FGFR-2 promoter region and used it to drive the expression of plasmids encoding the bacterial CAT enzyme. Tr ansfection of these plasmids into FGF treated and untreated cells did not produce significant variation in CAT activity, suggesting that FCF R-2 downregulation in response to ligand binding occurs mainly by a po st-transcriptional mechanism. In contrast, plasmids containing as litt le as 140 nt of the FCFR-2 promoter region were regulated in F9 cells, showing substantially higher expression in differentiated than in und ifferentiated cells. It appears therefore that FCFR-2 expression in fi broblasts and EC cells is regulated by somewhat different mechanisms. In contrast, FGFR-1 expression does not vary substantially under the c onditions shown to affect FGFR-2 expression. The implications of these findings are discussed. (C) 1995 Wiley-Liss, Inc.