Fibroblast growth factor receptors 1 and 2 are differentially regulated in murine embryonal carcinoma cells and in response to fibroblast growth factor-4.
We have studied the expression of two of the receptors for fibroblast growth factors, FGFR-1 and FGFR-2, in response to ligand binding and in 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 FGFR-1 mRNA appears unaffected. Furthermore, FGF-4 transformed cells display low levels of FGFR-2 mRNA and these levels are significantly increased by treatment with anti FGF-4 neutralizing antibodies. In undifferentiated F9 EC cells, the levels of FGFR-2 mRNA are very low and increase substantially upon induction of differentiation. 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. Transfection of these plasmids into FGF treated and untreated cells did not produce significant variation in CAT activity, suggesting that FGFR-2 downregulation in response to ligand binding occurs mainly by a post-transcriptional mechanism. In contrast, plasmids containing as little as 140 nt of the FGFR-2 promoter region were regulated in F9 cells, showing substantially higher expression in differentiated than in undifferentiated cells. It appears therefore that FGFR-2 expression in fibroblasts and EC cells is regulated by somewhat different mechanisms. In contrast, FGFR-1 expression does not vary substantially under the conditions shown to affect FGFR-2 expression. The implications of these findings are discussed.
Ali
J
J
Department of Microbiology, New York University School of Medicine, New York 10016, USA.
Mansukhani
A
A
Basilico
C
C
D000818:Animals; D001483:Base Sequence; D018236:Carcinoma, Embryonal / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors