Cell transformation by Int-2--a member of the fibroblast growth factor family.
The sequence similarities between Int-2 and members of the fibroblast growth factor (FGF) family have prompted functional as well as structural comparisons with other FGFs. Here we examine the ability of int-2 sequences to induced morphological transformation of NIH3T3 cells, a characteristic property of the secreted FGFs, such as FGF-5 and Hst1/kFGF. Despite encoding a short signal sequence, which directs the product to the secretory pathway, mouse int-2 DNA is incapable of inducing foci of transformation in the standard transfection assay. However, when transfected cells are enriched by co-selection with the neomycin resistance gene, a proportion of the int-2-expressing cells display a transformed phenotype, including the ability to grow as colonies in soft agar and in defined medium. Analyses of int-2 RNA and protein in these cells suggest that transformation by int-2 may require a threshold level of expression, and that the subsequent phenotype is dependent on the level of int-2 protein present in the cells.
Goldfarb
M
M
Department of Biochemistry, Columbia University, New York, NY 10032.
Deed
R
R
MacAllan
D
D
Walther
W
W
Dickson
C
C
Peters
G
G
D000818:Animals; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000494:pharmacology*; D013539:Simian virus 40 / Q000235:genetics; D014162:Transfection
C496444:FGF3 protein, human; C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors