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Query: UNIPROT:P14210 (hepatocyte growth factor)
 6,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocyte growth factor (HGF) is an important paracrine regulator for liver growth, whereas it inhibits growth of tumor cells including hepatocellular carcinoma. In contrast, transforming growth factor alpha (TGF alpha) is a factor which stimulates hepatocyte growth and causes hepatocellular carcinoma in an autocrine fashion. To determine whether TGF alpha is affected by HGF, we examined the regulation of TGF alpha expression in response to exogenous HGF in HepG2 cells. We first examined TGF alpha mRNA and protein in the presence of HGF and found nearly a 3.6-fold increase in mRNA and a 2.5-fold increase in TGF alpha protein. This induction was dose-dependent and followed delayed kinetics. Nuclear run-on experiments suggested that the mechanism for this induction was an increase in transcription of TGF alpha mRNA. These data suggest that HGF may modulate TGF alpha expression and the interaction of these cytokines may play an important role in liver diseases.
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PMID:Hepatocyte growth factor regulates transforming growth factor alpha in HepG2 hepatic cells. 817 88

We have identified a motility factor in conditioned medium of human fibroblasts that stimulates the migration of HepG2 cells in the Boyden chamber assay. This factor, termed epitaxin, was purified to homogeneity by ammonium sulfate precipitation, hydrophobic interaction chromatography on phenyl-Sepharose, and a series of reverse phase high performance liquid chromatography. Under a nonreducing condition, purified epitaxin migrated as a 36-kDa band, and the biological activity was recovered from the area in the gel coinciding with this band. Purified epitaxin stimulates the motility of HepG2 cells in the concentrations above 1 ng/ml with half-maximal activity at 4.2 ng/ml, and its mode of action is mainly chemotactic. Epitaxin slightly stimulates DNA synthesis of HepG2 cells, while scatter factor/hepatocyte growth factor which also stimulates the motility of HepG2 cells showed a growth-inhibitory effect. Epitaxin increases the motility of a wide variety of epithelially derived tumor cell lines, but none of the tested fibroblast lines responded to epitaxin. These results define epitaxin as a novel fibroblast-derived factor that affects the migration, and possibly the invasion, of epithelially derived tumor cells.
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PMID:Purification and biological characterization of epitaxin, a fibroblast-derived motility factor for epithelial cells. 818 13

The met protooncogene product, Met, is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). NIH 3T3 cells express HGF/SF endogenously and become tumorigenic in nude mice via an autocrine mechanism when murine Met is expressed ectopically (Metmu cells) or when human Met and human HGF/SF are coexpressed (HMH cells). Here, we show that Metmu and HMH cells are invasive in vitro and display enhanced protease activity necessary for the invasive phenotype. In experimental and spontaneous metastasis assays, Metmu or HMH cells metastasize to the lung, but lower numbers of subcutaneously injected Metmu and HMH cells produced invasive tumors in the heart, diaphragm, salivary gland, and retroperitoneum. It has been reported elsewhere that Met expression increased with tumor passage in athymic nude mice, and these tumor explants show enhanced activity in the metastasis assays. Autocrine-mediated Met-HGF/SF signal transduction in NIH 3T3 mesenchymal cells may provide an important system for understanding the biological process of metastasis.
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PMID:Invasiveness and metastasis of NIH 3T3 cells induced by Met-hepatocyte growth factor/scatter factor autocrine stimulation. 819 26

The proto-oncogene c-met encodes a heterodimeric (alpha, beta) tyrosine kinase receptor which binds the hepatocyte growth factor (HGF). Recently, overexpression of the Met/HGF receptor gene has been detected in fresh samples of carcinomas and in epithelial tumor cell lines but not in cell lines derived from human leukemia and lymphoma. Our analysis of 50 primary samples of human leukemia and lymphoma and 23 hematopoietic cell lines revealed expression of mRNA and protein of the met/HGF receptor in 6 out of the 73 hematopoietic tumor samples analyzed. Four of the six samples positive for expression of the Met/HGF receptor gene were derived from patients with Hodgkin's disease. In addition, in one Burkitt's lymphoma cell line and in one acute myeloid leukemia (AML), expression of the Met/HGF receptor gene was detected. In normal unstimulated lymphocytes, granulocytes or monocytes we did not find expression of the Met/HGF receptor gene. Upon stimulation with the phorbol ester TPA we detected a weak expression of Met/HGF receptor specific transcripts of 9.0 kb in peripheral blood mononuclear cells of a healthy donor. Cytogenetic analyses of three of the four cell lines which express the Met/HGF receptor gene revealed structural or numerical abnormalities of the long arm of chromosome 7, where the Met/HGFR gene is located, in each of the three cell lines analyzed. In one of these cell lines (L540) the Met/HGFR gene is translocated to a marker chromosome. Southern blot and pulsed field gel electrophoresis experiments did not show any rearrangement in a region of 600 kb around the Met/HGF receptor gene excluding an activation of Met/HGFR by a TPR/Met oncogenic rearrangement as described for MNNG-HOS cells and for some gastric tumors. Our data indicate that the Met/HGFR gene is deregulated in a few cases of human leukemia, Burkitt's lymphoma and Hodgkin's disease possibly by chromosomal rearrangements resulting in an overexpression of the normal Met/HGF receptor mRNA and protein without formation of a hybrid gene.
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PMID:The Met/hepatocyte growth factor receptor (HGFR) gene is overexpressed in some cases of human leukemia and lymphoma. 828 71

Hepatocyte growth factor (HGF) is a novel mitogen for mature hepatocytes. In the present study, we have measured immunoreactive (ir)-HGF concentration in tumor extracts of 82 primary human breast cancers using an enzyme-linked immunosorbent assay (ELISA). Ir-HGF was detectable in all tissue extracts, the concentration ranging from 1.4 to 306.5 ng/100 mg protein (median value: 11.2 ng/100 mg protein). Correlation analyses between ir-HGF concentration and clinicopathological factors showed that the ir-HGF level was significantly higher in tumors with sizes of more than 5.0 cm compared with those less than 5.0 cm. In contrast, no detectable amount of ir-HGF was secreted into culture medium of two breast cancer cell lines, MCF-7 and ZR-75-1, suggesting that the cancer cell itself has no ability to produce ir-HGF.
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PMID:Immunoreactive hepatocyte growth factor is present in tissue extracts from human breast cancer but not in conditioned medium of human breast cancer cell lines. 830 95

IMR-90 human embryonic lung fibroblasts secrete a tumor cytotoxic factor. This factor, termed F-TCF, is moderately cytotoxic in human tumor cell lines (KB, MCF-7, BG-1) and is very cytotoxic in mouse tumor cell lines (Sarcoma 180, Meth A sarcoma, P388). The cytotoxicity depends on the initial target cell number and is due to cytostasis rather than cytolysis. F-TCF was purified from conditioned medium by a combination of UF-concentration, CM sephadex C-50, Con A sepharose, Mono S cation-exchange and heparin sepharose chromatography and exhibited a molecular mass (M(r)) of 76 to 80 kD on SDS-PAGE under non-reducing conditions. F-TCF is a heterodimer composed of a large alpha-subunit with M(r) 52 to 56 kD and a small beta-subunit with M(r) 30 to 34 kD. F-TCF is a heparin-binding, heat-labile, basic glycoprotein (pI 7.4-8.6). Its activity is stable over the pH range of 6.0 to 9.0, but is completely lost after reduction with 2-mercaptoethanol. Protein sequencing indicates that the alpha-subunit is blocked at the aminoterminus. The primary amino acid sequences deduced from hepatocyte growth factor (HGF) cDNAs cloned from human placenta and liver cDNA libraries indicate that F-TCF is identical to the placenta type HGF in the aminoterminal sequence of the beta-subunit, but differs at two sites from the liver type HGF. Two forms of F-TCF cDNA were found in an IMR-90 human fibroblast cDNA library. One form was identical to placenta type HGF cDNA and the other was a variant with a 15 base pair deletion in the coding region. In addition, mRNA corresponding to the deleted form of cDNA was present in total RNA prepared from IMR-90 cells. F-TCF was thus identified as placenta type HGFs including a variant. The deleted form of recombinant HGF (rHGF) expressed in CHO cells had slightly lower heparin-binding affinity than did the intact form. Both rHGFs had almost the same dose-response curves for cytotoxicity in Sarcoma 180 or Meth A sarcoma cells. Moreover, rHGF (the deleted form) was cytotoxic in hepatocellular carcinoma cells (HepG2, Hep3B, H35). Dose-response curves for the stimulation of DNA synthesis in rat hepatocytes by HGFs were very similar up to about 12.5 ng/ml, but differed significantly at higher concentrations. The deleted form gave maximal activity in a dose range of 12.5 to 100 ng/ml and had about 1.4- to 1.9-fold higher specific activity in that range than the intact form did.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tumor cytotoxic activity of HGF-SF. 838 Jul 42

Hepatocyte growth factor (HGF), a mesenchymal-derived polypeptide, stimulates growth, motility and morphogenesis of various types of cells, most predominantly of epithelial cells. We have now identified an additional biological activity of HGF; this factor probably has a role in early hematopoiesis. We examined the effects of HGF on the growth of various murine hematopoietic progenitor tumor cell lines and found that HGF stimulated DNA synthesis in the myeloid leukemia cell line, NFS-60. The mitogenic effect of HGF on NFS-60 cells was additive with the effect of interleukin 3 (IL-3). On the other hand, HGF had no apparent effect on other myeloid leukemia cell lines examined, such as DA-3 and FDC-P1 cells. Scatchard analysis of specific binding of [125I]HGF revealed expression of a high-affinity HGF receptor on NFS-60 and DA-3 cells, but not on FDC-P1 cells. Expression of c-met mRNA correlated well with the existence of a high-affinity HGF receptor. Since the myeloid leukemia cell lines used are cells in the early stage of myeloid differentiation, HGF may play a role in early hematopoiesis.
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PMID:Hepatocyte growth factor stimulates growth of hematopoietic progenitor cells. 839 36

We have previously shown that, in mouse NIH/3T3 cells, it is necessary to coexpress the gene for human hepatocyte growth factor/scatter factor (HGF/SFhu) with its receptor, the human met protooncogene (methu), to activate the transforming activity of the receptor (S. Rong, M. Bodescot, D. Blair, T. Nakamura, K. Mizuno, M. Park, A. Chan, S. Aaronson, and G. F. Vande Woude, Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that exceptionally high levels of the ligand and its receptor are expressed in tumor cell explants after several tumor passages through nude mice. Confluent tumor cells explanted after the second passage in nude mice can express 1700 units/ml/10(6) cells/72 h of scatter activity as determined in Madin-Darby canine kidney cell scatter assays. The motogenic factor produced by these cells is easily purified by heparin-Sepharose chromatography, and the purified factor efficiently induces tyrosine phosphorylation of Methu in YaOvBix2NMA human ovarian carcinoma cells. To account for the unusually high level of HGF/SFhu and Methu expression, we propose that normal levels of Methu receptor are inefficient at transducing the signal(s) required for transformation of mouse cells. Therefore, high levels of Methu receptor are required for tumorigenesis, and corresponding high levels of the ligand are required to induce the signal. Consistent with this model, endogenous mouse scatter factor is not detected in conditioned medium from cells transformed by overexpression of the Metmu receptor.
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PMID:Tumorigenesis induced by coexpression of human hepatocyte growth factor and the human met protooncogene leads to high levels of expression of the ligand and receptor. 839 96

Hepatocyte growth factor (HGF) was first described as a hepatotrophic factor in partially hepatectomized rat plasma in the early 1980's and was purified from plasma of a patient with fulminant hepatic failure and from rat platelets in 1986-1987. Recent progress has revealed that HGF is the same protein as scatter factor and tumor cytotoxic factor, and is now known to be a broad-spectrum growth factor which stimulates cell growth not only of hepatocytes but also of many other types of epithelial and endothelial cells. In this review, however, we concentrate on the role of HGF, mainly human HGF, on liver regeneration after injury. In humans, plasma levels of hHGF increase to greater than 10 ng/ml during severe liver disease such as fulminant hepatic failure and decrease rapidly to normal levels when the patients recover from the disease. In less severe liver damage such as occurs in acute hepatitis, levels of hHGF in plasma increase to 0.5-1 ng/ml which is approaching the half maximal concentration for the stimulation of DNA synthesis in human hepatocytes in culture. Thus, HGF is believed to be involved in control of liver regeneration. Although the cell type(s) which produces HGF during liver disease is not yet identified, it is possible that circulating leukocytes or splenocytes are responsible. Synthesis of HGF is though to be regulated by a putative inducer(s) derived from damaged liver tissue. A control mechanism for HGF production during liver disease is proposed.
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PMID:The role of HGF-SF in animal and human hepatic physiology and pathology. 842 46

Hepatocyte growth factor is a multi-functional protein that elicits different biological responses in a tissue- or cell-specific manner. We have isolated the cDNA and gene for a previously unidentified protein that has the identical domain composition as hepatocyte growth factor. We have called this novel protein "hepatocyte growth factor-like protein". Both proteins contain four kringle domains followed by a serine protease-like domain. Overall, the two proteins are only about 50% identical. The human gene for hepatocyte growth factor-like protein has been localized to locus p21 on chromosome 3, where one or more tumor suppressor genes may be located. Although the biological function of HGF-like protein has not been determined we have localized the major site of synthesis to the liver. Whether this newly identified member of the hepatocyte growth factor family of proteins is involved in the development and differentiation of the liver remains to be determined.
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PMID:Genomic organization, chromosomal localization and developmental expression of hepatocyte growth factor-like protein. 842 50


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