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 hepatocyte growth factor (HGF) receptor, Met, has established oncogenic properties; however, its expression and function in esophageal adenocarcinoma (EA) remain poorly understood. We aimed to determine the expression and potential alterations in Met expression in EA. Met expression was investigated in surgical specimens of EA, Barrett's esophagus (BE), and normal esophagus (NE) using immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction. Met expression, phosphorylation, and the effect of COX-2 inhibition on expression were examined in EA cell lines. IHC demonstrated intense Met immunoreactivity in all (100%) EA and dysplastic BE specimens. In contrast, minimal immunostaining was observed in BE without dysplasia or NE specimens. Met mRNA and protein levels were increased in three EA cell lines, and Met protein was phosphorylated in the absence of serum. Sequence analysis found the kinase domain of c-met to be wild type in all three EA cell lines. HGF mRNA expression was identified in two EA cell lines. In COX-2-overexpressing cells, COX-2 inhibition decreased Met expression. Met is consistently overexpressed in EA surgical specimens and in three EA cell lines. Met dysregulation occurs early in Barrett's dysplasia to adenocarcinoma sequence. Future study of Met inhibition as a potential biologic therapy for EA is warranted.
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PMID:The HGF receptor c-Met is overexpressed in esophageal adenocarcinoma. 1572 Aug 19

Differentiation of adult bone marrow (BM) cells into nonhematopoietic cells is a rare phenomenon. Several reports, however, suggest that human umbilical cord blood (hUCB)-derived cells give rise to hepatocytes after transplantation into nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice. Therefore, we analyzed the hepatic differentiation potential of hUCB cells and compared the frequency of newly formed hepatocyte-like cells in the livers of recipient NOD-SCID mice after transplantation of hUCB versus murine BM cells. Mononuclear cell preparations of hUCB cells or murine BM from enhanced green fluorescent protein transgenic or wild-type mice were transplanted into sublethally irradiated NOD-SCID mice. Liver regeneration was induced by carbon tetrachloride injury with and without subsequent hepatocyte growth factor treatment. By immunohistochemistry and reverse transcriptase-polymerase chain reaction, we detected clusters of hepatocyte-like cells in the livers of hUCB-transplanted mice. These cells expressed human albumin and Hep Par 1 but mouse CK18, suggesting the formation of chimeric hepatocyte-like cells. Native fluorescence microscopy and double immunofluorescence failed to detect single hepatocytes derived from transplanted enhanced green fluorescent protein-transgenic mouse BM. Fluorescent in situ hybridization rarely revealed donor-derived hepatocyte-like cells after cross-gender mouse BM transplantation. Thus, hUCB cells have differentiation capabilities different from murine BM cells after transplantation into NOD-SCID mice, demonstrating the importance of further testing before hUCB cells can be used therapeutically.
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PMID:Human cord blood stem cells generate human cytokeratin 18-negative hepatocyte-like cells in injured mouse liver. 1604 39

Various in vivo studies demonstrated a migration tendency of neural stem cells (NSCs) toward gliomas, making these cells a potential carrier for delivery of therapeutic genes to disseminated glioma cells. We analyzed which factors determine NSC migration and invasion in vitro. Conditioned media prepared from 10 different human glioma cell lines, as well as 13 different tumor-associated growth factors, were analyzed for their chemotactic effects on murine C17.2 NSCs. The growth factor receptor status was analyzed by reverse transcriptase-polymerase chain reaction. Invasion of NSCs into multicellular tumor spheroids generated from 10 glioma cell lines was quantified. NSCs displayed a heterogeneous migration pattern toward glioma spheroids as well as toward glioma-cell-conditioned medium. Chemotactic migration was stimulated up to fivefold by conditioned medium as compared to controls. In coculture assays, NSC invasion varied from single cell invasion into glioma spheroids to complete dissemination of NSCs into glioma spheroids of different cell lines. Among 13 different growth factors, scatter factor/hepatocyte growth factor (SF/HGF) was the most powerful chemoattractant for NSCs, inducing a 2.5-fold migration stimulation. An antibody against SF/HGF inhibited migratory stimulation induced by conditioned media. NSC migration can be stimulated by various growth factors, similar to glioma cell migration. The extent to which NSCs infiltrate three-dimensional glioma cell aggregates appears to depend on additional factors, which are likely to include cell-to-cell contacts and interaction with extracellular matrix proteins.
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PMID:Neural stem cell migration toward gliomas in vitro. 1621 12

In this study, we demonstrate the ability of a three-dimensional co-culture model to preserve some key aspects of differentiated hepatocyte function in vitro. Freshly isolated rat hepatocytes in co-culture with activated stellate cells rapidly aggregate to form well-defined viable spheroids. After 5 days in culture, the spheroids have a complex extracellular matrix support and hepatic ultrastructure including bile canaliculi, tight junctions, desmosomes and lipid storage. Co-culture spheroids have superior cytochrome P450 (CYP450) 3A and 2B function, and increased inducibility of 2B function, relative to a range of hepatocyte monoculture techniques (high-performance liquid chromatography of testosterone metabolites). Increased function in co-culture is supported by greater expression of CYP450 3A23, 1A2, and 2E1 mRNA relative to monoculture (reverse transcriptase quantitative polymerase chain reaction). Also, high hepatocyte growth factor mRNA expression in co-culture suggests a post-traumatic, or possibly regenerative, environment. A preliminary study of human hepatocytes co-cultured with rat stellate cells demonstrated prolonged function of CYP450 3A4, 2C19 and 2C9. This study shows that stellate cells facilitate spheroid formation, influence spheroid architecture, and are an effective method of preserving some aspects of hepatocyte function in the early stage of culture.
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PMID:The effect of three-dimensional co-culture of hepatocytes and hepatic stellate cells on key hepatocyte functions in vitro. 1653 1

The loss of cell cycle control in malignant melanomas is thought to be due to a lack of retinoblastoma protein (pRb) activity. We have recently reported a progressive deficiency of the retinoblastoma-binding protein 2-homolog 1 (RBP2-H1) in advanced and metastatic melanomas in vivo, suggesting a role of RBP2-H1 in loss of pRb-mediated control. Therefore, in this study, we re-established the pRb-modulating function of RBP2-H1 in highly metastatic A375-SM melanoma cells by re-expressing its C-term (cRBP2-H1). As previously shown, the corresponding domains comprise the pRb-binding region of the RBP2-H1 protein (non-T/E1A-pRb-binding domain (NTE1A)). As a result, we detected pRb-hypophosphorylation selectively at Ser795, but not at Ser780 and Ser807/811 throughout the G1 phase of the cell cycle. As a further consequence, a block in G1/S transition was observed accompanied by a significant decrease of DNA replication and cellular proliferation. As demonstrated by cDNA microarrays of cRBP2-H1-transduced cells and confirmed by quantitative TaqMan reverse transcriptase-PCR, differential expression of melanoma-progression-related genes was observed, among them bone morphogenetic protein 2, follistatin, transforming growth factor alpha, hepatocyte growth factor, transcription factor 4 and microphthalmia-associated transcription factor. Conclusively, these data suggest that RBP2-H1 exerts a broad tumor-suppressive function partially mediated by pRb modulation. Therefore, re-establishing of RBP2-H1 could evolve as an interesting novel approach in developing experimental treatments for metastatic melanomas.
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PMID:Re-expression of the retinoblastoma-binding protein 2-homolog 1 reveals tumor-suppressive functions in highly metastatic melanoma cells. 1664 88

The repair system of damaged biliary mucosa was not fully clarified so far in primary biliary cirrhosis (PBC). Given that related factors of the hepatocyte growth factor (HGF) such as HGF activator (HGFA) and HGFA inhibitor type 1 (HAI-1) participate in the repair of injured gastrointestinal mucosa, we investigated the involvement of the HGF/HGFA/HAI-1 system in PBC and control livers. The expression of HGFA, HAI-1, and c-Met was examined in PBC livers (n=24), diseased livers (control, n=30), and normal livers (n=15) by immunohistochemistry and semiquantitative reverse transcriptase-polymerase chain reaction. We examined the expression of HGFA, HAI-1, and c-Met, and the effect of HGF administration on cell proliferation and wound healing, and HAI expression in cultured mouse biliary epithelial cells (BECs). HAI-1 expression was faint in control livers, whereas it was significantly augmented in damaged small bile ducts, bile ductules, and periportal hepatocytes in PBC (p<0.05). HGFA and c-Met were homogeneously expressed in BECs in PBC and control livers. HAI-1 expression was increased at the front of wound healing and the treatment with HGF-enhanced HAI-1 expression, cell proliferation, and wound healing in cultured BECs. HGF/HGFA/HAI-1 system may participate in biliary mucosal repair as reported in gastrointestinal mucosal repair.
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PMID:Augmented expression of hepatocytes growth factor activator inhibitor type 1 (HAI-1) in intrahepatic small bile ducts in primary biliary cirrhosis. 1694 Nov 51

Neural tube defects (NTD) are morphogenetic alterations due to a defective closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic effects are mediated by signal transducers and activators of transcription (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in fetuses with NTD. By reverse transcriptase-polymerase chain reaction and immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and placentas. The reduced expression of this pathway correlated with the absence of p53 in all these samples. On the contrary, detectable expression levels of p53, HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained from the same fetuses. Comparable results were obtained by immunohistochemistry, with the exception of p53, which was undetected in all fetal tissues. In conclusion, in NTD fetuses, both the defective neural tube tissue and the placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade. This raises the possibility of using the suppression of these genes for early diagnosis of NTD especially on chorionic villus sampling.
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PMID:Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects. 1721 87

Hepatocyte growth factor (HGF) is a cytokine known to play multiple roles during the various stages of wound healing. This study addresses the ongoing key questions regarding the role of HGF in wound healing, namely: are HGF and its regulators expressed differently in chronic and acute wounds? Biopsies from normal skin (n=10), acute (n=10), and chronic wounds (n=17) were analyzed by immunohistochemistry, reverse transcriptase polymerase chain reaction (RT-PCR), and quantitative real-time RT-PCR for the presence of HGF, its receptor cMet, its activators and its inhibitors. Immunohistochemical staining for HGF, HGF activators, and HGF inhibitors was similar, with expression being greater in chronic wound dermis compared with acute wound dermis. While expression of cMet in chronic wound dermis was less than in the acute wound dermis. PCR quantification of these proteins showed similar trends although the differences did not reach statistical significance. The results of this study provide important data confirming the role of HGF in wound healing. In addition, we have demonstrated the aberrant expression of the HGF receptor cMet and activation inhibitors (HAI-1 and HAI-2) in chronic wounds. This aberrant expression may have a value in predicting the process of healing and nonhealing wounds and constitute important targets of future therapies.
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PMID:Hepatocyte growth factor regulation: an integral part of why wounds become chronic. 1797 Oct 14

The remarkable capacity of the liver to regenerate after injury and the prospects of organ self-renewal have attracted much interest in the understanding and modulation of the underlying molecular events. We investigated the effect of mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) on liver by correlating intravital microscopy, immunohistochemistry, and reverse transcriptase polymerase chain reaction in a rat model of 2/3 hepatectomy. RAPA significantly retarded proliferation of hepatocytes, endothelial cells, and hepatic stellate cells (HSCs) mostly between days 2 and 4 after hepatectomy and downregulated major cytokines and growth factors (tumor necrosis factor alpha, hepatocyte growth factor, platelet-derived growth factor, platelet-derived growth factor receptor, insulin-like growth factor-1, transforming growth factor beta 1) important for liver regeneration. These effects were almost absent at later time points. RAPA also had a transient, but broad effect on angiogenesis, and impaired sinusoidal density as well as mRNA levels of vascular endothelial growth factor, vascular endothelial growth factor receptor 1, vascular endothelial growth factor receptor 2, and angiopoietin-1. Activation of HSC was also transiently suppressed as observed by smooth muscle protein 1 alpha protein expression and intercellular adhesion molecule-1 mRNA levels. The rate of apoptosis in liver was significantly increased by RAPA between day 3 and day 7. The effect of RAPA on liver repair, angiogenesis, and HSC activation is confined to the phase of active cell proliferation. This transient effect might allow further exploration of mTOR inhibitors in clinical situations that involve liver regeneration, and seems to have implications beyond immunosuppression.
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PMID:Impact of rapamycin on liver regeneration. 1839 22

Hepatocyte growth factor (HGF) was initially identified in cultured hepatocytes and subsequently reported to induce angiogenic, morphogenic, and antiapoptotic activity in various tissues. These properties suggest a potential influence of HGF on bone healing. We asked if gene transfer of human HGF (hHGF) into an osteotomy gap with a hemagglutinating virus of Japan-envelope (HVJ-E) vector promotes bone healing in rabbits. HVJ-E that contained either hHGF or control plasmid was percutaneously injected into the osteotomy gap of rabbit tibias on Day 14. The osteotomy gap was evaluated by radiography, pQCT, mechanical tests, and histology at Week 8. The expression of hHGF was evaluated by reverse transcriptase-polymerase chain reaction and immunohistochemistry at Week 3. Radiography, pQCT, and histology suggested the hHGF group had faster fracture healing. Mechanical tests demonstrated the hHGF group had greater mechanical strength. The injected tissues at 3 weeks expressed hHGF mRNA by reverse transcriptase-polymerase chain reaction. hHGF-positive immunohistochemical staining was observed in various cells at the osteotomy gap at Week 3. The data suggest delivery of hHGF plasmid into the osteotomy gap promotes fracture repair, and HGF could become a novel agent for fracture treatment.
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PMID:Percutaneous nonviral delivery of hepatocyte growth factor in an osteotomy gap promotes bone repair in rabbits: a preliminary study. 1881 94


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