Biological significance of the hst-1 gene.
hst-1, or HSTF1 in human gene nomenclature, was originally identified as a transforming gene in DNA samples from human stomach cancer by NIH3T3 transfection assay. Many reports have followed to show the presence of a transforming hst-1 gene in various types of cancerous and noncancerous tissues, suggesting that the hst-1 gene is the most common non-ras transforming gene. We cloned the hst-1 genomic fragments from DNAs of a normal individual and a patient with leukemia and also from NIH3T3 cells themselves. All of these clones transformed NIH3T3 cells upon transfection. Sequence analysis of the cDNA and genomic hst-1 led us to conclude that the normal hst-1 protein transforms NIH3T3 cells when its expression is deregulated. The hst-1 protein has 40-50% homology to basic and acidic fibroblast growth factors (FGFs) and to the int-2 protein. The purified hst-1 protein synthesized in a baculovirus system was a potent heparin-binding growth factor for a variety of cells, including human endothelial cells. The hst-1 protein, when it was added to the culture medium, induced morphological transformation of NIH3T3 cells and anchorage-independent growth of NRK cells. The hst-1 gene is located 35 kbp downstream of one of its homologous genes, int-2, on human chromosome 11 at band q13.3. As in the case with the int-2 gene, the hst-1 transcripts were not detected in adult mice but found in mouse embryos. A relatively large amount of the hst-1 message was present in a mouse teratocarcinoma cell line, F9, while the int-2 mRNA was barely detected. Upon induction of differentiation in vitro, the hst-1 transcription was depressed to almost nil, and the int-2 message increased dramatically. The hst-1 and int-2 genes were coamplified in a variety of cancer cells, most notably in more than 50% of esophageal cancers.
Terada
M
M
National Cancer Center Research Institute, Tokyo, Japan.
Yoshida
T
T
Sakamoto
H
H
Miyagawa
K
K
Katoh
O
O
Hattori
Y
Y
Sugimura
T
T
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002880:Chromosomes, Human, Pair 11; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors; D005347:Fibroblasts; D006133:Growth Substances / Q000235:genetics* / Q000502:physiology; D006801:Humans; D051379:Mice; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D004273:DNA, Neoplasm; C496444:FGF3 protein, human; C496445:FGF4 protein, human; C489197:Fgf3 protein, mouse; C496446:Fgf4 protein, mouse; D051518:Fibroblast Growth Factor 3; D051519:Fibroblast Growth Factor 4; D006133:Growth Substances; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D004247:DNA