Biological significance of the hst-1 gene.

M. Terada, T. Yoshida, H. Sakamoto, K. Miyagawa, O. Katoh, Y. Hattori, T. Sugimura

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Abstract

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.

Original languageEnglish
Pages (from-to)71-80
Number of pages10
JournalPrincess Takamatsu symposia
Volume20
Publication statusPublished - 1989
Externally publishedYes

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Terada, M., Yoshida, T., Sakamoto, H., Miyagawa, K., Katoh, O., Hattori, Y., & Sugimura, T. (1989). Biological significance of the hst-1 gene. Princess Takamatsu symposia, 20, 71-80.