Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The met proto-oncogene receptor tyrosine kinase has been identified as a receptor for hepatocyte growth factor (HGF)/scatter factor (SF). HGF/SF is a multifunctional cytokine that stimulates mitogenesis, dissociation, and motility of a broad spectrum of epithelial and endothelial cells in culture, promotes the progression of carcinoma cells to a more invasive phenotype, and acts as a morphogenic factor for tubular epithelia. HGF/SF is predominantly expressed by mesenchymal cells, whereas the met/HGF/SFR is predominantly expressed by epithelial and carcinoma cells in culture. We have shown by Northern analyses that the met/HGF/SFR is expressed in many adult mouse tissues. To elucidate the normal physiologic role for the met/HGF/SFR and the possible pathologic consequences of deregulation of this pathway, we have examined the expression of the met/HGF/SFR in adult mouse tissue by in situ hybridization. We show that the met/HGF/SFR is generally expressed in epithelia, including hepatocytes, epithelial cells that line the proximal and distal convoluted tubules of the kidney, epithelia of stomach, esophagus, uterus, lung and skin, as well as in granulosa cells of developing and mature oocytes. By reverse transcriptase PCR amplification, we show that the HGF/SF gene is expressed at low levels in many of these tissues. Our data support a possible role for the met/HGF/SFR in epithelial cell growth and tissue organization.
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PMID:Expression of the hepatocyte growth factor/scatter factor receptor tyrosine kinase is localized to epithelia in the adult mouse. 747 19

Hepatocyte growth factor (scatter factor) and its receptor, the c-met proto-oncogene product (c-MET), have been implicated in embryogenesis, tissue reorganization, and tumor progression. Little is known, however, of the expression and functional significance of these molecules in prostatic cells and tissue. In this investigation, we assessed the expression of hepatocyte growth factor (HGF) and c-MET in prostatic tissues and cell lines and also determined the effect of purified recombinant HGF on cell proliferation and scattering of prostatic carcinoma cell lines. HGF was expressed by human prostatic stromal myofibroblasts in primary culture but not by three human prostatic carcinoma cell lines (LNCaP, DU 145, and PC-3) as assessed by Northern blot analysis. HGF was also detected by reverse transcriptase-polymerase chain reaction in both benign and malignant tissues from radical prostatectomy specimens. c-MET transcripts were identified by Northern blot in two androgen-insensitive human prostatic carcinoma cell lines (DU 145 and PC-3) but not the androgen-sensitive LNCaP cell line. Additional evidence of linkage of androgen responsiveness and c-MET was provided by experiments in which androgen deprivation of normal rat prostates via castration produced a marked up-regulation of c-MET expression as determined by Northern blot and immunohistochemistry. c-MET protein was detected by immunohistochemical analysis in a substantial percentage (58 of 128 or 45%) of prostatic carcinomas and was found more often in metastatic growths of human prostatic carcinoma (15 of 20 patients) compared with primary tumors (43 of 108 patients; P < 0.005). Moreover, in Dunning R-3327 rat prostatic carcinoma cell lines, c-MET expression was highest in the androgen-insensitive subline with the highest metastatic capacity. Purified recombinant human HGF induced dose-dependent cellular proliferation and scattering in the DU 145 carcinoma cell line. These data indicate that HGF may function in the prostate gland as a paracrine growth factor, with synthesis by stromal cells and with biological target cells being the epithelial cells. Expression of the HGF receptor, c-MET, is up-regulated by androgen deprivation and c-MET appears to be preferentially expressed on androgen-insensitive, metastatic cells, suggesting a possible linkage of c-MET expression with prostatic carcinoma progression.
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PMID:Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. 763 32

A cDNA encoding mouse hepatocyte growth factor (HGF) has been cloned and completely sequenced by use of reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent cloning. Sequence analysis reveals that mouse HGF, similar to its human and rat counterparts, consists of 728 amino acids, and both the alpha- and beta-chains are encoded in a single open reading frame. Strong homology exists in the primary structure of HGF among the three species of mouse, rat and human (more than 90%), especially in Kringle 1 of the alpha chain which is assumed to be an essential domain for binding of HGF to its receptor, c-MET, a proto-oncogene product. Our results suggest the existence of evolutionary pressure to conserve the distinct structure, and presumably the biological functions, of HGF.
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PMID:Molecular cloning and characterization of cDNA encoding mouse hepatocyte growth factor. 824 Dec 72

Hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-alpha) stimulate liver regeneration, whereas transforming growth factor beta 1 (TGF-beta 1) inhibits it in rats. However their significance in human liver diseases, especially in severe acute liver injury, remains unclear. We studied HGF, TGF-alpha, and TGF-beta 1 messenger RNA (mRNA) expression in the livers of patients with live diseases using a competitive reverse transcriptase polymerase chain reaction. As little as a twofold difference in mRNA expression could be detected from minute liver biopsy samples. We then examined cell proliferation using proliferating cell nuclear antigen (PCNA) staining. HGF mRNA levels were significantly higher (approximately threefold) in acute hepatitis (AH) than in exacerbation of chronic liver disease (EX) (P < .05). TGF-alpha mRNA levels were significantly greater in AH (approximately twofold) than EX (P < .05), and the levels were significantly higher (approximately threefold) in chronic hepatitis (CH) than in EX (P < .05). The TGF-beta 1 mRNA levels in all the groups were not significantly different. In acute liver injury (AH and EX), there was a significant correlation between HGF mRNA expression and the PCNA labeling index (LI) in the liver (r = .87, P < .005). TGF-alpha mRNA expression also correlated with the PCNA LI (r = .92,P < .0001). There was no significant correlation between the serum HGF and the PCNA LI in the liver. In conclusion, HGF and TGF-alpha produced in the liver stimulate hepatocyte proliferation in response to acute liver injury in humans.
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PMID:Expression of hepatocyte growth factor, transforming growth factor alpha, and transforming growth factor beta 1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation. 869 Apr

Myeloma cell line supernatants were screened for their ability to inhibit the activity of transforming growth factor-beta (TGFbeta) in the mink lung cell (Mv-1-Lu) bioassay. Supernatant from the human myeloma cell line JJN-3 contained potent TGFbeta antagonistic activity. This activity was isolated and found to be associated with a 72-78-kDa glycoprotein. Specific polyclonal and monoclonal antibodies were generated toward the 72-78-kDa protein, and these antibodies precipitated the TGFbeta inhibitory activity from JJN-3 supernatant. Upon amino acid sequencing the protein appeared to be identical to hepatocyte growth factor (HGF), and some of the generated antibodies directly blocked the action of recombinant HGF in various assays. By HGF-specific polymerase chain reaction we demonstrated that HGF mRNA was expressed in five out of five tested myeloma cell lines. The level of HGF protein in supernatants showed great variation from >500 ng/ml in JJN-3 supernatant to a few ng/ml in the supernatants from other myeloma cell lines. The same five cell lines were also screened for expression the HGF receptor c-MET. Four of them expressed the receptor as shown by reverse transcriptase-polymerase chain reaction and Western blot. The receptor was shown to be constitutively phosphorylated in the human myeloma cell line JJN-3. This receptor could be dephosphorylated by anti-HGF antibodies, indicating the existence of an autocrine HGF loop in this cell line. We propose that HGF/c-MET may play a role in multiple myeloma.
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PMID:Concomitant expression of hepatocyte growth factor/scatter factor and the receptor c-MET in human myeloma cell lines. 879 32

We have examined whether the hepatocyte growth factor (HGF)/c-met receptor-ligand pair is expressed in freshly isolated and highly purified myeloma cells and whether HGF can be found in the sera of myeloma patients. Myeloma cells were purified with an immunomagnetic method using the syndecan 1-specific antibody B-B4. HGF and c-met mRNA in these cells were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). HGF and c-met proteins were detected by enzyme-linked immunosorbent assay (ELISA) and Western blot, respectively. Serum from 13 myeloma patients was obtained at diagnosis and the levels of HGF were determined by ELISA. HGF and c-met mRNA were expressed in all examined samples (n = 7). HGF was detected in the supernatants of 17 of 20 primary cultures of myeloma cells, whereas bone marrow mononuclear cells from normal controls did not produce detectable amounts of HGF (n = 3). The mean HGF level in serum of myeloma patients at diagnosis was more than fourfold higher than the mean level in normal controls. Possible implications of HGF/c-met expression for the pathophysiology of multiple myeloma are discussed.
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PMID:Hepatocyte growth factor and its receptor c-met in multiple myeloma. 891 66

Scatter factor (SF), also known as hepatocyte growth factor, is angiogenic in systemic tissue, and SF titers correlate with the malignancy and metastatic phenotype of certain systemic cancers. Human gliomas express SF and its receptor c-met, but their role in the malignant progression of these tumors has not been defined. To examine this, 9L glioma cells that express c-met but not SF were transfected with human SF cDNA, and their behavior in vitro and in vivo was examined. SF gene expression was detected in conditioned medium of 9L-SF but not in control 9L-neo-transfected cell lines, by reverse transcriptase-PCR, immunoblot, ELISA, and scatter activity assays. Gliomas derived from 9L-SF and control 9L-neo cell lines implanted in the caudate/putamen of Fisher 344 rats (intracranially) and in the flanks of SCID/Beige mice (subcutaneously) were examined. Extracts from intracranial (i.c.) gliomas contained elevated levels of SF protein as determined by ELISA (1 to 5.5 ng SF/mg protein), whereas no SF was detected in control tumors. Reverse transcriptase-PCR of RNA from i.c. gliomas revealed that only 9L-SF gliomas expressed SF and both 9L-neo and 9L-SF gliomas expressed the c-met SF receptor. By postimplantation Day 14, 9L-SF i.c. gliomas were approximately 5-fold larger than 9L-neo control tumors (p < 0.001). Subcutaneous 9L-SF glioma growth was also greater than that in controls, although the differences were more variable. SF-producing i.c. gliomas contained elevated levels of 48-kd urokinase (3.5-fold) and 92-kd type IV collagenase (2.8-fold), both enzymes that correlate with the malignant progression of human gliomas (p < 0.001). SF-producing and control 9L cell lines did not differ in rates of proliferation, thymidine incorporation, or adhesion-independent growth in vitro. Conditioned medium from 9L-SF cells stimulated thymidine incorporation into microvessel brain endothelial cells 3- to 4-fold higher than did CM from 9L-neo controls (p < 0.001). Intracranial 9L-SF gliomas were more angiogenic than controls based on elevated peak (2.25-fold; p < 0.005) and mean (1.7-fold; p < 0.008) blood vessel densities. These results suggest that SF production by glioma cells enhances glioma malignancy in vivo, in part, by paracrine mechanisms involving glioma-associated angiogenesis.
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PMID:Scatter factor/hepatocyte growth factor gene transfer enhances glioma growth and angiogenesis in vivo. 911 17

Hepatocyte growth factor/scatter factor (HGF/SF) is secreted by mesenchymal cells and elicits proliferation, motility, differentiation, and morphogenesis of epithelia and other cells. These effects are mediated by binding to MET, a receptor tyrosine kinase. Genetically engineered mice lacking HGF/SF die in utero due to a failure of placental and hepatocyte differentiation, but little information exists regarding the expression of this signaling system in human development. Using reverse transcriptase-polymerase chain reaction, Western blots, and immunohistochemistry, we report that HGF/SF and MET are expressed during critical early periods of human organogenesis from 6 to 13 wk of gestation. Organs that expressed both genes included liver, metanephric kidney, intestine, and lung, each of which develop by inductive interactions between mesenchyme and epithelia. Of all organs studied, the placenta contained the highest levels of HGF/SF protein, and MET was detected in trophoblastic cells of chorionic villi as early as the 5th wk of gestation. Finally, examination of a human multicystic dysplastic kidney demonstrated that malformed, hyperproliferative tubules expressed MET, whereas HGF/SF protein was immunolocalized to the same epithelia and also to the surrounding undifferentiated cells. Hence HGF/SF might be an important growth factor in normal human embryogenesis and may additionally play a role in human organ malformations.
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PMID:Expression of hepatocyte growth factor/scatter factor and its receptor, MET, suggests roles in human embryonic organogenesis. 912 88

The Met protooncogene encodes the tyrosine kinase receptor for the hepatocyte growth factor (HGF), a potent mitogen for hepatocytes and other epithelial cells produced by mesenchymal cells. Many of the studies on the physiologic and neoplastic growth of the liver, as well as other organs, have been performed in the rat. Therefore, chromosomal mapping of the rat Hgf gene and the gene of its receptor is of particular value. To achieve this, a probe of the coding part of rat HGF cDNA was used to isolate four genomic probes from a lambda phage rat genomic library. These probes were used to map the Hgf gene to Chromosome (Chr) 4q12 by the FISH technique. To obtain a probe for the mapping of the HGF receptor/Met gene, we cloned the complete coding region of the rat HGF receptor mRNA. Complementary DNA (cDNA) was synthesized with reverse transcriptase from total RNA for use as a template for the PCR. The two PCR primers were designed based on human and mouse sequences and were located in the flanking regions of the open reading frame of the HGF receptor mRNA. Amplification resulted in a band of an estimated size of 4.1 kb, which was cloned and sequenced. The nucleotide sequence showed about 93% and 85% homology compared with mouse and human HGF receptor sequences, respectively. A full-length probe of the coding part of the cDNA was used to map the rat HGF receptor/Met gene to Chr 4q21 by the FISH technique. Therefore, the rat Hgf and HGF receptor/Met genes are located relatively close to each other, in a way similar to humans but not mice.
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PMID:Chromosomal localization of rat hepatocyte growth factor (Hgf) and HGF receptor (Met) and characterization of HGF receptor cDNA. 927 68

Hepatocyte growth factor acts differently depending on the organs or tumours involved. It may be produced simultaneously with its receptor, c-Met, in several types of malignant tumour cells and may exercise an autocrine regulation. To analyse the effect of hepatocyte growth factor in human prostate cancer, we conducted immunohistochemistry, in situ hybridization and the reverse transcriptase polymerase chain reaction. The first two techniques revealed the growth factor in prostate cancer cells, and the polymerase chain reaction confirmed this expression. c-Met is expressed in prostate cancer cells, but not in interstitial cells. Hepatocyte growth factor is expressed in interstitial cells, especially in hormone-treated cancer tissue, indicating that the growth factor pathway changes with the hormonal status. Low-grade tumours expressed c-Met at the plasma membrane. Higher grade tumours tended to express it in the cytoplasm, suggesting that the role of c-Met as the hepatocyte growth factor receptor was blocked in higher grade tumours. The relationship between the growth factor and its receptor is thus influenced by hormonal status and differentiation in prostate cancer and is not explained simply in terms of autocrine or paracrine action.
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PMID:Co-expression of hepatocyte growth factor and its receptor in human prostate cancer. 953 4


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