Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have demonstrated previously a pronounced increase in the expression of hepatocyte growth factor (HGF) (Z. Hu, R. P. Evarts, K. Fujio, E. R. Marsden, and S. S. Thorgeirsson, Am. J. Pathol., 142: 1823-1830, 1993), transforming growth factor alpha (TGF-alpha) (R. P. Evarts, H. Nakatsukasa, E. R. Marsden, Z. Hu, and S. S. Thorgeirsson, Mol. Carcinog., 5: 25-31, 1992), and acidic fibroblast growth factor (aFGF) (E. R. Marsden, Z. Hu, K. Fujio, H. Nakatsukasa, S. S. Thorgeirsson, and R. P. Evarts, Lab. Invest., 67: 427-433, 1992) that coincided with the proliferation and differentiation of putative hepatic stem cells and perisinusoidal stellate (Ito) cells. Here, we examine the earliest stages of stem cell activation in rat liver using an experimental model involving treatment with acetylaminofluorene and partial hepatectomy (R. P. Evarts, P. Nagy, E. Marsden, and S. S. Thorgeirsson, Carcinogenesis (Lond.), 8: 1737-1740, 1987). Histochemical identification of stem cell progeny and Ito cells was accomplished by OV6 and desmin antibodies, respectively. Expression of the 2.1-kilobase alpha-fetoprotein transcripts and the concomitant DNA synthesis ([3H]thymidine label) were used as indicators for the activation of the stem cell compartment. Expression of HGF, TGF-alpha, and aFGF was analyzed at the time of partial hepatectomy and 4, 12, 24, 48, 72, and 92 h after the operation. [3H]-Thymidine-labeled OV6- and desmin-positive cells were present in the portal space and in the Glisson capsule 4 h after partial hepatectomy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of hepatic stem cell compartment in the rat: role of transforming growth factor alpha, hepatocyte growth factor, and acidic fibroblast growth factor in early proliferation. 769 Nov 52

The met protooncogene tyrosine kinase receptor (Met) and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), ordinarily constitute a paracrine signaling system in which cells of mesenchymal origin produce the ligand, which binds to the receptor that is predominantly expressed in cells of epithelial origin. However, mouse NIH/3T3 fibroblasts overexpressing Met induce tumor formation in nude mice via an autocrine mechanism (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that human cell lines established from various sarcomas express high levels of activated Met receptor. HGF/SF is also detected in the human sarcoma cell lines but at a reduced level when compared to primary fibroblasts. These properties, high Met expression and reduced ligand levels, are indistinguishable from the properties of NIH/3T3 tumor explant cells overexpressing Met (S. Rong et al., Mol. Cell. Biol., 12: 5152-5158, 1992; S. Rong et al., Cell Growth & Differ., 4: 563-569, 1993). Moreover, paraffin-embedded sections of primary tumors from human osteosarcomas, chondrosarcomas, and leiomyosarcoma stain intensely for Met and/or HGF/SF and display extensive tumor cell heterogeneity with regard to both paracrine and autocrine stimulation. On the basis of these findings, we propose that Met-HGF/SF autocrine signaling may contribute to the tumorigenic process in human sarcomas.
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PMID:Met expression and sarcoma tumorigenicity. 769 39

Scatter factor/hepatocyte growth factor (SF/HGF) stimulates the motility of epithelial cells, initially inducing centrifugal spreading of cell colonies followed by disruption of cell-cell junctions and subsequent cell scattering. These responses are accompanied by changes in the actin cytoskeleton, including increased membrane ruffling and lamellipodium extension, disappearance of peripheral actin bundles at the edges of colonies, and an overall decrease in stress fibers. The roles of the small GTP-binding proteins Ras, Rac, and Rho in regulating responses to SF/HGF were investigated by microinjection. Inhibition of endogenous Ras proteins prevented SF/HGF-induced actin reorganization, spreading, and scattering, whereas microinjection of activated H-Ras protein stimulated spreading and actin reorganization but not scattering. When a dominant inhibitor of Rac was injected, SF/HGF- and Ras-induced spreading and actin reorganization were prevented, although activated Rac alone did not stimulate either response. Microinjection of activated Rho inhibited spreading and scattering, while inhibition of Rho function led to the disappearance of stress fibers and peripheral bundles but did not prevent SF/HGF-induced motility. We conclude that Ras and Rac act downstream of the SF/HGF receptor p190Met to mediate cell spreading but that an additional signal is required to induce scattering.
Mol Cell Biol 1995 Feb
PMID:Regulation of scatter factor/hepatocyte growth factor responses by Ras, Rac, and Rho in MDCK cells. 782 27

Hepatocyte growth factor (HGF) stimulates growth of mature hepatocytes, whereas it inhibits growth of cancer cells including hepatocellular carcinoma (HCC) cells. However, the regulatory mechanisms for this phenomenon remains unclear. An important intermediary in HGF signal transduction in normal hepatocytes, c-myc, was not induced in FaO HCC cells after HGF stimulation, suggesting that intracellular signalling pathways of HGF in FaO HCC cells were different from those in normal hepatocytes. Protein kinase C (PKC) has been reported to be involved in signalling pathways of many growth factors. To study whether PKC is associated with this inhibitory mechanism, we studied the effects of HGF and/or 12-O-tetradecanoyl phorbol-13-acetate (TPA) on the growth of normal hepatocytes and FaO HCC cells. Consequently, HGF or TPA stimulated growth of normal hepatocytes, while equal doses of TPA or HGF inhibited growth of FaO HCC cells, respectively. In addition, TPA reversed the HGF effect in both normal hepatocytes and FaO HCC cells. These data suggest that an inhibitory effect of HGF on FaO HCC cells may be associated with changes of protein kinase C-mediated intracellular signalling pathways.
Res Commun Mol Pathol Pharmacol 1994 Sep
PMID:Inhibitory effect of hepatocyte growth factor against FaO hepatocellular carcinoma cells may be associated with changes of intracellular signalling pathways mediated by protein kinase C. 782 2

We sought to determine whether the hepatocyte growth factor/scatter factor (HGF/SF)- and keratinocyte growth factor-receptor systems were expressed in normal breast cells, breast carcinoma cell lines, normal breast tissues, and breast cancer tissues. Reverse transcriptase-polymerase chain reaction and hot blotting were used to detect HGF, HGF/SF (met) receptor, KGF, and KGF receptor mRNAs in human mammary epithelial (HME) and stromal (HMS) cells. We also examined breast carcinoma (MDA-MB-157, SCC 38, and SCC 70) and spontaneously immortalized breast epithelial (HMT 3522) cell lines, as well as normal breast and breast carcinoma tissues. PCR products were also confirmed by nucleic acid sequencing. The effects of HGF and KGF, compared to EGF and heparin-binding EGF, on the proliferation of normal human mammary epithelial cells in serum-free defined medium was determined by cell counting. HGF and KGF mRNAs were detected in HMS cells, but not HME cells. KGF receptor mRNA was detected in HME cells, but not HMS cells. HGF/SF receptor mRNA was detected in both HME and HMS cells. mRNAs were also detected in normal breast and breast carcinoma tissues, as well as breast carcinoma and transformed breast epithelial cell lines. Alternative cDNA sequences that are predicted to code for a soluble KGF receptor and a membrane bound, truncated HGF/SF receptor were detected in breast epithelial cells and breast tissues. HGF and KGF maintained viability and stimulated proliferation of HME cells.
Cell Mol Biol Res 1994
PMID:Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and their receptors in human breast cells and tissues: alternative receptors. 786 34

Hepatocyte growth factor (HGF) was originally identified as an hepatotrophic factor inducing liver regeneration, and was also recently found to stimulate mitogenesis of various epithelial cells. In the present study, we examined the mitogenic effects of native and recombinant HGF on cells of rat visceral glomerular epithelial cell line (SGE1). Native and recombinant HGF each stimulated DNA synthesis in and growth of SGE1 cells to a remarkable degree. These mitogenic activities were dose-dependent, being detectable at 2.5 ng/ml and maximal at 20 ng/ml. Over 30% of SGE1 cells tested were shifted to S-phase by HGF alone, as judging by labeling index values. DNA synthesis stimulated by native or recombinant HGF was high at low SGE1 cell density and was strongly suppressed at high cell density. DNA synthesis in and growth of SGE1 cells were stimulated more strongly by recombinant HGF than by native HGF. In addition, the effects of recombinant HGF and epidermal growth factor were additive, while transforming growth factor-beta 1 strongly inhibited the stimulation of DNA synthesis by recombinant HGF. These findings suggest that HGF may play a role in controlling visceral glomerular epithelial cell growth.
Cell Mol Biol (Noisy-le-grand) 1994 Dec
PMID:Hepatocyte growth factor is a potent promoter of mitogenesis in cultured rat visceral glomerular epithelial cells. 787 82

Hepatocyte growth factor (HGF), a cytokine with multiple functions, exhibits cell-type-specific as well as cytokine- and steroid hormone-regulated expression. The HGF gene is known to be expressed predominately in mesenchymal but not in epithelial cells. In this study, we report the identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse HGF gene, which is evidently responsible for the suppression of HGF expression in epithelial cells. Gel mobility shift assays and DNase I footprinting studies revealed that a 27-bp element (-16 to +11) around the transcription initiation site is responsible for the binding of a nuclear protein which is present in epithelial but not in mesenchymally derived cells. Further analysis of the binding activity of the DNA region with nuclear protein revealed that an approximately 19-bp sequence containing a unique palindromic structure (5'-AACCGACCGGTT-3') overlapped by a CAP box is essential for binding. Substitution of a single base (the contact site) within this region by site-directed mutagenesis resulted in total abrogation of the binding of the nuclear protein and a concomitant increase in the transcriptional activity of various lengths of HGF-chloramphenicol acetyltransferase fused genes when transfected into the epithelial cell line RL95-2 but not the mesenchymal cell line NIH 3T3. Southwestern (DNA-protein) analyses revealed that the nuclear protein which binds to this repressor element is a single polypeptide of approximately 70 kDa. Analysis of the nuclear extract prepared from regenerating mouse liver at various times after two-thirds partial hepatectomy by gel mobility shift assay revealed a substantial reduction (more than 75% within 3 h) in the binding of the repressor to its cognate binding site. Our results suggest that a cis-acting transcriptional repressor in the promoter region of the mouse HGF gene is involved in cell-type-specific regulation through binding to its cognate trans-acting protein which exists in epithelial cells but is absent in fibroblast cells.
Mol Cell Biol 1994 Nov
PMID:Identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse hepatocyte growth factor gene. 793 20

Based upon findings that the scatter factor/hepatocyte growth factor (SF/HGF) has strong mitogenic and motogenic properties, and that the sperm cell acquires its fertilizing capacity and motility in the distal parts of mammalian epididymis, the present study was conducted to investigate the role of SF/HGF in initiation of sperm cell motility. This was investigated by determining the expression of SF/HGF in various regions of the murine male genital tract by scatter and cell tracking assays using MDCK epithelial cells, Western blot procedure, and the immunohistochemical procedure using paraffin sections of various regions of the male genital tract. The findings from all these assays indicate that SF/HGF is differentially expressed in various parts of the male genital tract with slight or no expression in the testes, caput epididymis, and vas deferens, and with the highest expression in cauda and corpus (distal) epididymis followed by expression in the corpus (proximal) epididymis. This region-specific SF/HGF expression pattern coincides with the pattern of acquiring the fertilizing capacity and motility by the sperm cell during its transit through the male genital tract. However, wherever SF/HGF was expressed in the male genital tract, its molecular weight was slightly higher (Mr, 82 kD), compared to the SF/HGF expressed in various other somatic tissues (Mr, 78 kD), indicating that the genital tract SF/HGF may be a different molecular species that shares some immunoreactive epitopes with the somatic cell SF/HGF. Incubation of immotile sperm from caput epididymis with the purified human placental SF/HGF of 78 kD initiated motility in 5-15% of sperm population. These results strongly suggest that the SF/HGF-like activity is expressed in the male genital tract in a region-specific manner, and this activity may have a role in initiation of sperm motility acquired during its transit through the epididymis in mammals.
Mol Reprod Dev 1994 Aug
PMID:Expression of scatter factor/hepatocyte growth factor is regionally correlated with the initiation of sperm motility in murine male genital tract: is scatter factor/hepatocyte growth factor involved in initiation of sperm motility? 798 Sep 52

Hepatocyte growth factor (HGF) is expressed in a variety of tissues and cell types under normal conditions and in response to various stimuli such as tissue injury. In the present study, we demonstrate that the transcription of the HGF gene is stimulated by estrogen in mouse ovary. A single injection of 17 beta-estradiol results in a dramatic and transient elevation of the levels of mouse HGF mRNA. Sequence analysis has found that two putative estrogen responsive elements (ERE) reside at -872 in the 5'-flanking region and at +511 in the first intron, respectively, of the mouse HGF gene. To test whether these ERE elements are responsible for estrogen induction of HGF gene expression, chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness. Transfection results indicate that the ERE elements of the mouse HGF gene can confer estrogen action to either homologous or heterologous promoters. Nuclear protein extracts either from RL95-2 cells transfected with the estrogen receptor expression vector or from mouse liver bound in vitro to ERE elements specifically, as shown by band shift assay. Therefore, our results demonstrate that the HGF gene is transcriptionally regulated by estrogen in mouse ovary; and such regulation is mediated via a direct interaction of the estrogen receptor complex with cis-acting ERE elements identified in the mouse HGF gene.
Mol Cell Endocrinol 1994 Sep
PMID:Modulation of hepatocyte growth factor gene expression by estrogen in mouse ovary. 798 45

We recently developed transgenic mice expressing hepatocyte growth factor (HGF) specific to hepatocytes. Hepatocytes of HGF transgenic mice showed a 2-fold increase of DNA labeling indices in vivo compared with those of wild type mice. To assess in vitro growth potential of hepatocytes from HGF transgenic mice, we studied the effects of epidermal growth factor (EGF), insulin or transforming growth factor beta (TGF beta) on DNA synthesis of hepatocytes derived from HGF transgenic or wild type mice, respectively. We found that DNA synthesis of hepatocytes from HGF transgenic mice was significantly enhanced, compared with that from wild type mice, respectively, and that its effect was additive with EGF or insulin. Further, growth-inhibitory effects of TGF beta on hepatocytes was greatly depressed in transgenic mice-derived hepatocytes, compared with that in wild type hepatocytes. These data suggest that the autocrine action of HGF is a potent stimulus for hepatocyte growth, and stress its importance as regulator of liver regeneration.
Res Commun Mol Pathol Pharmacol 1994 Aug
PMID:Assessment of in vitro growth potential of hepatocytes expressing hepatocyte growth factor in an autocrine fashion. 799 59


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