Molecular biology of the hst-1 gene.

The hst-1 gene (or HSTF1 by human gene nomenclature) was originally identified in our laboratory by an NIH/3T3 focus formation assay using DNA from a human gastric cancer. Sequence analysis predicted the hst-1 product to be a novel growth factor with 30-50% homology with six other heparin-binding growth factors: basic and acidic fibroblast growth factors (FGFs), the int-2 protein, FGF5, the hst-2/FGF6 protein and keratinocyte growth factor (KGF). A recombinant hst-1 protein was synthesized in silkworm cells and found to be a potent heparin-binding mitogen for murine fibroblasts and human vascular endothelial cells. Although hst-1 expression cannot be detected in most cancer cells, including gastric cancers, it is expressed in mouse embryos and in some germ cell tumours. Both hst-1 and int-2 are located on band q13.3 of human chromosome 11 within a distance of 35 kbp; in the mouse genome these two genes are separated by less than 20 kbp. They are differentially transcribed in the F9 mouse teratocarcinoma cell line; hst-1 is expressed in undifferentiated stem cells and int-2 in differentiated endodermal cells. The hst-1 and int-2 genes were coamplified in a variety of cancer cells, most notably in more than 50% of oesophageal cancers.