Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer.

Abstract

The human HSTI gene, previously designated the hst gene, and now assigned the name HSTFI for heparin-binding secretory transforming factor in human gene nomenclature, was originally identified as a transforming gene in DNAs from human stomach cancers by transfection assay with mouse NIH 3T3 cells. The amino acid sequence of the product deduced from DNA sequences of the HSTI cDNA and genomic clones had approximately 40% homology to human basic and acidic fibroblast growth factors and mouse Int-2-encoded protein. We have mapped the human HSTI gene to chromosome 11 at band q13.3 by Southern blot hybridization analysis of a panel of human and mouse somatic cell hybrids and in situ hybridization with an HSTI cDNA probe. The HSTI gene was found to be amplified in DNAs obtained from a stomach cancer and a vulvar carcinoma cell line, A431. In all of these samples of DNA, the INT2 gene, previously mapped to human chromosome 11q13, was also amplified to the same degree as the HSTI gene.

Association of INT2/HST1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis

“…Amplification of the 1 1q13 region have been reported from various solid tumours including, besides breast cancer, squamous cell carcinomas (Zhou et al, 1988, Berenson et al, 1989, a stomach cancer and the vulvar carcinoma cell line A431 (Yoshida et al, 1988a), melanomas (Adelaide et al, 1988, bladder and Oesophageal carcinomas (Tsutsumi et Tsuda et al, 1988;, and a hepatocellular carcinoma (Hatada et al, 1988). It usually entails the INT2 and HSTJ genes and also the BCLI locus, recognised as a chromosomal breakpoint in B-cell leukaemia (Tsujimoto et al, 1984), but not other genes located at the same or neighbouring bands (Ali et al, 1989).…”

“…The HST pORFI probe recognised four constant ECORI digested DNA fragments (Figure 2). The three shortest fragments (5.8, 2.8 and 0.8 kb) harbour the HSTJ gene, while the largest fragment (8.0 kb) represents binding to the HST2 gene (Yoshida et al, 1988a Steriod receptor analysis Measurements of Oestrogen (ER) and progesterone receptors (PgR) were performed within two weeks after surgery, at one laboratory and with radioligand binding techniques (isoelectric focusing and dextran-coated charcoal (DCC) with Scatchard analysis, respectively) as described previously (Norgren et al, 1982). The isoelectric focusing assay has previously been shown to be eqivalent to the DCC assay for ER measurement (Ferno et al, 1983).…”

K-sam, an amplified gene in stomach cancer, is a member of the heparin-binding growth factor receptor genes.

“…Increased cellular DNA content is often associated with advanced malignancy (1,2). Yet, only a limited amount of information is available on genetic changes involved in stomach cancers, which have the highest incidence among malignant diseases worldwide (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Amplification of asyet-unrecognized genes was expected to occur in stomach cancer, especially in the late stage of carcinogenesis.…”

Elimination of extrachromosomally amplified MYC genes from human tumor cells reduces their tumorigenicity.

“…Since amplification of genes such as NMYC, Her2/ neu, and MYC has been correlated with a poor prognosis (2)(3)(4)(5), it is reasonable to infer that the overexpression of such genes contributes to tumor cell growth or survival. Furthermore, while amplification of a specific gene such as Her2/neu occurs in only 25% of human breast cancer (3)(4)(5), the total incidence ofamplification in breast cancer exceeds 70% when those tumors with MYC (5), hst-int-PRADI (6,7), and bcll amplification are included. If overexpression of each of these genes contributes to tumorigenicity, then strategies to decrease their expression may retard tumor growth.…”