Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14210 (hepatocyte growth factor)
 6,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor-beta 1 (TGF-beta 1) inhibited secretion of human hepatocyte growth factor (hHGF), which is also known as scatter factor or fibroblast-derived tumor cytotoxic factor, by MRC-5 cells. The effect was detectable at as little as 10 pg/ml and was more potent than that of dexamethasone. Complete inhibition was observed after 12 h in the presence of 5 ng/ml of TGF-beta 1. Phorbol 12-myristate 13-acetate-induced secretion of hHGF from human skin fibroblasts was also suppressed by TGF-beta 1. TGF-beta 2 inhibited hHGF secretion by MRC-5 cells to the same extent as TGF-beta 1, but other growth factors such as epidermal growth factor and acidic and basic fibroblast growth factors had only a slight or null inhibitory effect.
 ...
PMID:TGF-beta is a potent inhibitor of hepatocyte growth factor secretion by human fibroblasts. 142 59

Fibroblast-derived tumor cytotoxic factor (F-TCF), isolated from human embryonic lung fibroblasts, is cytotoxic against various human and mouse tumor cells. Physicochemical and biological properties indicate that F-TCF is closely similar to hepatocyte growth factors (HGFs), cDNAs of which are isolated from human liver and placenta. Isolation and expression of F-TCF cDNA revealed that F-TCF was identical to the placenta type HGFs, including a variant with a deletion of 15 base pairs in the coding region. The deleted form of recombinant HGF (rHGF) had slightly lower heparin binding affinity than the intact form. Specific activities of rHGFs were almost the same in tumor cytotoxic activity, but different in hepatocyte growth stimulating activity. These results indicate that deletion of five amino acids results in conformational change which alter biological activity.
 ...
PMID:[Structure and biological property of fibroblast-derived tumor cytotoxic factor (F-TCF)]. 143 88

To evaluate the role of protein phosphorylation reactions in signal transduction of human hepatocyte growth factor (hHGF), now known to be the same protein as the scatter factor and tumor cytotoxic factor, we examined the effects of various inhibitors of protein kinases on the mitogenic activity of hHGF on rat hepatocytes in primary culture. Genistein, a specific inhibitor of tyrosine kinase, dose-dependently inhibited the effect of hHGF in stimulating DNA synthesis of hepatocytes. By contrast, 1-(5-isoquinolinesulfonyl)-2- methylpiperazine (H7), a specific inhibitor of protein kinase C, potentiated the stimulatory effect of hHGF on DNA synthesis of hepatocytes. H7 was effective at over 2 micrograms/ml and potentiated the effect of hHGF over 2-fold at 20 micrograms/ml. On the other hand, an inhibitor of Ca++/calmodulin-dependent protein kinase inhibited both the basal and hHGF-stimulated DNA synthesis in the cells, whereas an inhibitor of cyclic nucleotide-dependent protein kinases had little effect on the action of hHGF. These results suggest that tyrosine phosphorylation is required for stimulation of hepatocyte DNA synthesis by hHGF and that the action of hHGF is negatively regulated by protein kinase C activation.
 ...
PMID:Effects of protein kinase inhibitors on the mitogenic activity of human hepatocyte growth factor on rat hepatocytes in primary culture. 153 55

A human genomic DNA library was screened by using conditions of reduced stringency with a bovine cDNA probe coding for the kringle domains in prothrombin in order to isolate the human prothrombin gene. Twelve positives were identified, three of which coded for prothrombin (Degen & Davie, 1987). Phage L5 was characterized in more detail because of its strong hybridization to the cDNA probe and its unique restriction map compared to the gene coding for human prothrombin. The gene in L5 was sequenced and found to code for a kringle-containing protein. A human liver cDNA library was screened by using a genomic probe from the gene in L5. cDNAs were isolated that contained sequence identical with regions in the gene in L5. Comparison of the cDNA with the gene indicated that the gene in L5 was composed of 18 exons separated by 17 intervening sequences and is 4690 bp in length. Exons ranged in size from 36 to 242 bp in length while intervening sequences ranged from 77 to 697 bp in length. The putative protein encoded by the gene in L5 contains four kringle domains followed by a serine protease-like domain. This domain structure is identical with that found in hepatocyte growth factor (HGF), although the two proteins are only about 50% identical. On the basis of the similarity of the protein encoded by L5 and HGF, we propose that the putative L5 protein be tentatively called HGF-like protein until a function is identified. The DNA sequence of the gene and cDNA and its translated amino acid sequence were compared against GenBank and NBRF databases. Sequences homologous to DNF15S1 and DNF15S2, human DNF15S2 lung mRNA, and rat acyl-peptide hydrolase were identified in exon 17 to the 3' end of the characterized sequence for the gene. From our results, it is apparent that the gene coding for human HGF-like protein is located at the DNF15S2 locus on human chromosome 3 (3p21). The gene for acyl-peptide hydrolase is 444 bp downstream of the gene coding for HGF-like protein, but on the complementary strand. The DNF15S2 locus has been proposed to code for one or more tumor suppressor genes since this locus is deleted in DNA from small cell lung carcinoma, other lung cancers, renal cell carcinoma, and von Hippel-Lindau syndrome.
 ...
PMID:Characterization of the DNF15S2 locus on human chromosome 3: identification of a gene coding for four kringle domains with homology to hepatocyte growth factor. 165 21

Hepatocyte growth factor (HGF) has potent mitogenic activity for mature hepatocytes and various normal epithelial cells. We now have evidence that HGF at 1-10 ng/ml, strongly inhibits the growth of HepG2 hepatocellular carcinoma cells, B6/F1 melanoma cells and KB squamous carcinoma cells. These tumor cells express high affinity receptors for HGF with a Kd of 25-28 pM, similar to findings with hepatocytes. HGF at 1-100 ng/ml had no significant cytolytic effect on tumor cells. Therefore, the anti-proliferative effect of HGF on tumor cells seems to be cytostatic, not cytolytic. As HGF apparently has bidirectional effects on cell growth, the possibility that it can serve as an anti-tumor agent merits attention.
 ...
PMID:Hepatocyte growth factor has potent anti-proliferative activity in various tumor cell lines. 165 43

Studies with hepatocyte cultures have defined four hepatocyte mitogens which can transmit a complete mitogenic signal in cultures kept in completely defined conditions. These four mitogens are epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), hepatopoietin A/hepatocyte growth factor (HPTA/HGF) and hepatopoietin B (HPTB). In this study, we investigated the effect of aFGF, HGF and the mito-inhibitor transforming growth factor beta (TGF-beta) on cultured hepatocytes isolated from livers of rats treated with the xenobiotic hepatic tumor promoters phenobarbital (PB) and alpha-hexachlorocyclohexane (alpha-HCH). Male F344 rats were treated with each of these two xenobiotics to stimulate hepatic DNA synthesis and augmentative hepatomegaly. At different times on the regimens with tumor promoters, hepatocytes were isolated and placed in primary culture. DNA synthesis of hepatocytes in culture stimulated by these two growth factors and the suppression of DNA synthesis affected by TGF-beta were examined as a function of time of treatment in vivo with these two promoters. Following day 10, hepatocytes from both promoter regimens became unresponsive to these two growth factors for the rest of the duration of the treatment (day 90). TGF-beta suppressed DNA synthesis stimulated by growth factors but did not affect the high background DNA synthesis stimulated by xenobiotics themselves.
 ...
PMID:Long-term treatment with hepatic tumor promoters inhibits mitogenic responses of hepatocytes to acidic fibroblast growth factor and hepatocyte growth factor. 171 12

Scatter factor (SF) is a fibroblast-derived cytokine which stimulates motility of epithelial and vascular endothelial cells. We used a quantitative assay based on migration of cells from microcarrier beads to flat surfaces to study the regulation of motility in bovine brain endothelial cells (BBEC). Peptide growth factors (EGF, ECGF, basic FGF) did not stimulate migration. Tumor promoting phorbol esters (PMA, PDD) markedly stimulated migration, while inactive phorbol esters (4a-PDD, phorbol-13,20-diacetate) did not affect migration. Both SF- and PMA-stimulated migration were inhibited by 1) TGF-beta; 2) protein kinase inhibitors (e.g., staurosporine, K-252a); 3) activators of the adenylate cyclase signaling pathway (e.g., dibutyryl cyclic AMP, theophylline); 4) cycloheximide; and 5) anti-cytoskeleton agents (e.g., cytochalasin B, colcemid). However, PMA and SF pathways were distinguishable: 1) PMA induced additional migration at saturating SF concentrations; 2) the onset of migration-stimulation was immediate for PMA and delayed for SF; and 3) down-modulation of protein kinase C (PKC) ablated PMA but not SF responsiveness. Assessment of PKC by (3H)-phorbol ester (PDBu) binding and by immunoblot showed 1) scatter factor does not cause significant redistribution or down-modulation of PDBu binding or alpha-PKC; and 2) PDBu mediates redistribution and down-modulation of both binding and alpha-PKC. These findings suggest two pathways for BBEC motility: a PKC-dependent pathway and an SF-stimulated/PKC-independent pathway.
 ...
PMID:Regulation of motility in bovine brain endothelial cells. 182 64

We previously demonstrated that a tumor cytotoxic factor(F-TCF) purified from the culture broth of human embryonic lung diploid fibroblast, IMR-90 cells was one of the human hepatocyte growth factors (hHGFs). In the present report, we demonstrate its biological functions. F-TCF showed moderate cytotoxicity on human tumor cell lines KB, BG-1, MCF-7 and Hs913 T, and strong cytotoxicity on mouse tumor cell lines Sarcoma 180, Meth A sarcoma and P388. On the contrary, F-TCF was a potent mitogen not only for adult rat hepatocytes, but also for human endothelial cells, HUVEC and human melanocytes. Moreover, F-TCF induced the differentiation of premyelocyte leukemia, HL-60 cells into morphologically granulocyte-like cells. These biological functions suggest that F-TCF is an effector molecule responsible for inflammation and repair in injured tissues including tumor and liver.
 ...
PMID:A fibroblast-derived tumor cytotoxic factor/F-TCF (hepatocyte growth factor/HGF) has multiple functions in vitro. 183 76

The acquisition of invasive properties by transformed epithelial cells constitutes an essential step in the progression of carcinomas. We have defined 2 types of interferences leading to enhanced motility and invasiveness of epithelial cells: (i) disturbances of intercellular adhesion, and (ii) treatment with "scatter factor", a secretory protein of mesenchymal cells. Invasive properties (invasion of collagen gels or embryonal heart tissue) are acquired by epithelial cells in vitro when intercellular adhesion is inhibited by antibodies that are specific for the cell-cell adhesion molecule E-cadherin. Furthermore, we found that differentiated human carcinoma cell lines are noninvasive and express E-cadherin, whereas dedifferentiated carcinoma lines are invasive and have lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin antibodies. A correlation between the degree of tumor differentiation and the amount of E-cadherin expression was also visualized on frozen sections of ovarian carcinomas, lobular breast carcinomas, and squamous carcinomas of head and neck. Thus, loss of E-cadherin appears to be a critical step in the establishment of an invasive, i.e. fully malignant phenotype. Scatter factor, which is also capable of dissociating epithelial cell colonies in vitro, was isolated from conditional medium of human fibroblasts; it is a 92,000 mol.wt glycoprotein, which is proteolytically cleaved into 62,000 and 34/32,000 mol.wt subunits. The purified glycoprotein induces invasion of MDCK cells into collagen matrices, and induces or enhances the invasive properties of various human carcinoma cell lines. Sequencing of tryptic peptides of scatter factor revealed strong similarity with hepatocyte growth factor. Furthermore, both factors exhibit identical activities, i.e. scatter factor stimulates DNA synthesis of primary hepatocytes and hepatocyte growth factor dissociates and increases the motility of various epithelial cells. Thus scatter factor and hepatocyte growth factor represent identical or closely similar proteins.
 ...
PMID:The role of E-cadherin and scatter factor in tumor invasion and cell motility. 183 25

For determination of fibroblast-derived tumor cytotoxic factor, F-TCF (human hepatocyte growth factor/hHGF), sensitive two-step sandwich enzyme-linked immunosorbent assay (ELISA) employing monoclonal antibodies was developed. Microplates were coated with monoclonal antibody (P1C8) and bound F-TCF was quantitated with the second monoclonal antibody (P2D6) linked to peroxidase. The standard curve for F-TCF was found to be linear in the range of 0.16 to 10 ng of F-TCF per ml. The assay was specific for F-TCF but not for plasminogen. The assay can be used for determination of F-TCF antigen in both human plasma and serum. The variation of absorbance was little in duplicate samples. Recoveries of exogenous F-TCF added to serum or plasma samples showed theoretical values. F-TCF antigen levels in 21 healthy volunteers was found to be 0.56 +/- 0.43 ng/ml. In contrast, mean F-TCF levels in patients with liver diseases were all higher than those of healthy subjects. This ELISA system has the advantage of using a sensitive and reproducible set of monoclonal antibodies, and is a useful method for monitoring F-TCF levels in patients with liver diseases.
 ...
PMID:ELISA for F-TCF (human hepatocyte growth factor/hHGF)/fibroblast-derived tumor cytotoxic factor antigen employing monoclonal antibodies and its application to patients with liver diseases. 183 58


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>