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The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors
1Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Abstract:
We previously described the isolation of a human oncogene which had acquired transforming potential by a DNA rearrangement accompanying transfection of NIH 3T3 cells with human tumor DNA (X. Zhan, A. Culpepper, M. Reddy, J. Loveless, and M. Goldfarb, Oncogene 1:369-376, 1987). We now term this oncogene the FGF-5 gene, since it specifies the fifth documented protein related to fibroblast growth factors (FGFs. Two regions of the FGF-5 sequence, containing 122 of its 267 amino acid residues, were 40 to 50% homologous to the sequences of acidic and basic FGFs as well as to the sequences of the FGF-related oncoproteins int-2 and hst/KS3. The FGF-5 gene bears the three exon structures typical for members of this family. FGF-5 was found to be expressed in the neonatal brain and in 3 of the 13 human tumor cell lines examined. Several experiments strongly suggested that FGF-5 is a growth factor with properties common to those of acidic and basic FGFs. The rearrangement which activated the FGF-5 gene during DNA transfection had juxtaposed a retrovirus transcriptional enhancer just upstream from the native promoter of the gene.
Insights
Researchers identified the FGF-5 gene, a human oncogene activated by DNA rearrangement. This gene encodes a protein similar to fibroblast growth factors (FGFs) and shows growth factor properties.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- A human oncogene with transforming potential was previously identified following DNA transfection.
- This oncogene's activation involved a DNA rearrangement in NIH 3T3 cells using human tumor DNA.
Purpose of the Study:
- To characterize the newly identified human oncogene, now termed FGF-5.
- To investigate the sequence homology, structure, expression, and function of the FGF-5 gene and its encoded protein.
Main Methods:
- DNA sequence analysis to determine homology with known fibroblast growth factors (FGFs).
- Examination of gene structure, including exon organization.
- Analysis of gene expression in neonatal tissues and human tumor cell lines.
- Functional assays to assess growth factor properties.
Main Results:
- The oncogene was named FGF-5, specifying the fifth protein related to FGFs.
- FGF-5 sequence showed 40-50% homology to acidic and basic FGFs and related oncoproteins.
- FGF-5 possesses a typical three-exon structure common to this gene family.
- FGF-5 expression was detected in neonatal brain and in a subset of human tumor cell lines.
- Experiments indicated FGF-5 functions as a growth factor with properties similar to FGFs.
- The activating DNA rearrangement placed a retroviral enhancer upstream of the FGF-5 promoter.
Conclusions:
- FGF-5 is a novel member of the fibroblast growth factor family, identified as a human oncogene.
- The gene's activation during transfection was mediated by enhancer-promoter interaction.
- FGF-5 has the potential to act as a growth factor, contributing to oncogenesis.