Identification of a novel human fibroblast growth factor and characterization of its role in oncogenesis.
The fibroblast growth factor (FGF) family of signaling molecules has been implicated in normal developmental and physiological processes, as well as in human malignancy. Using a homology-based genomic DNA mining process, we identified a human gene encoding a novel member of the FGF family, that we designate FGF-20. The FGF-20 cDNA was isolated, and its sequence confirmed the gene prediction. FGF-20 is expressed in normal brain, particularly the cerebellum, and in some cancer cell lines. Recombinant FGF-20 protein induces DNA synthesis in a variety of cell types and is recognized by multiple FGF receptors. Ectopic expression of FGF-20 in NIH 3T3 cells renders the cells transformed in vitro and tumorigenic in nude mice. These results underscore the utility of mining genomic DNA databases and reveal FGF-20 to be a novel oncogene that may play a role in human cancer.
Jeffers
M
M
CuraGen Corporation, New Haven, Connecticut 06511, USA. mjeffers@curagen.com
Shimkets
R
R
Prayaga
S
S
Boldog
F
F
Yang
M
M
Burgess
C
C
Fernandes
E
E
Rittman
B
B
Shimkets
J
J
LaRochelle
W J
WJ
Lichenstein
H S
HS
D016475:3T3 Cells / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D014162:Transfection; D014981:Xenopus
D018076:DNA, Complementary; C416003:FGF20 protein, human; C498812:Fgf20 protein, mouse; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D004247:DNA