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)

Five rat hepatoma cell lines were shown to secrete hepatocyte-stimulating factors (HSFs) capable of inducing a characteristic spectrum of acute phase genes. Three of these lines, but not normal rat livers or livers from rats with an experimentally induced acute inflammation, produced interleukin 6 (IL6) mRNA. An anti-rat IL6 serum was prepared against synthetic peptides derived from the rat IL6 cDNA sequence. This antiserum cleared authentic rat IL6 and a fraction of the HSF activities secreted by the hepatoma cell lines. After concentration of culture supernatants from FTO2B hepatoma cells, IL6 was detected with the anti-IL6 serum by immuno-blot analysis. Biosynthesis of IL6 in the HTC line was demonstrated by metabolic labeling and immunoprecipitation. Secretion of HSF activities by hepatoma cells was increased by serum factors. These data suggest that different rat hepatoma lines each secrete different characteristic sets of HSF activities and establish unambiguously that IL6 is secreted by at least some of these lines.
Mol Biol Med 1990 Jun
PMID:Production of interleukin 6 by hepatoma cells. 169 11

A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists.
Mol Cell Biol 1990 Dec
PMID:Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family. 170 Oct 20

Rat T-kininogen (T-KG), a cysteine protease inhibitor, is an acute phase reactant which is induced to high levels in response to inflammation. Both hormones and cytokines participate in this regulation. To investigate the cis-acting elements responsible for the induction of gene expression, various 5'-fragments of the rat T-KG gene were fused to a chloramphenicol acetyltransferase marker gene. These constructs were transfected into a rat hepatoma cell line which was then treated with tumor necrosis factor or interleukin-6 or both cytokines. Expression of the chloramphenicol acetyltransferase gene was induced with interleukin-6 treatment, but suppressed by tumor necrosis factor. The 5'-region of the T-KG gene responsible for conferring both of these effects was localized between nucleotides -404 to -210 upstream of the transcription start site. Fragments containing this region were found to be effective in either orientation, and could also regulate a heterologous promoter.
Mol Endocrinol 1990 Apr
PMID:Differential regulation of rat T-kininogen by tumor necrosis factor and interleukin-6. 170

Binding proteins for the insulin-like growth factors (IGFBP) are important modulators of the biological actions of IGF-I and IGF-II. Concentrations of one of these proteins, IGFBP-1, in human plasma and IGFBP-1 mRNA in rat liver are markedly altered in diabetes and fasting. We now examine the regulation of IGFBP-1 and IGFBP-I mRNA in H4-II-E cells, a rat cell line derived from the minimal deviation H35 Reuber hepatoma previously reported to synthesize IGFBP-1 as its predominant IGF-binding protein. Confluent H4-II-E cells in serum-free medium were incubated with different hormones for 48 h, and the conditioned medium was analyzed by ligand blotting. Dexamethasone (10(-6) M) increased levels of 30-kDa IGFBP-1 approximately 10-fold; stimulation was half-maximal at 6 x 10(-9) M dexamethasone. No stimulation was seen with progesterone, testosterone, IGF-I, or rat GH, whereas insulin gave a small inhibition. Immunoblot analysis using a monoclonal antibody to human IGFBP-1 confirmed that the 30-kDa IGFBP induced by dexamethasone was IGFBP-1. IGFBP-1 mRNA was increased to a similar extent (7-fold), as determined by Northern blot hybridization using human or rat IGFBP-1 cDNA probes. The stimulation of IGFBP-1 mRNA was observed within 3 h after the addition of dexamethasone; IGFBP-1 in the medium increased more slowly. After withdrawal of dexamethasone from stimulated cells, IGFBP-1 mRNA decreased by 80% after 48 h; IGFBP-1 decreased more slowly. The increased abundance of IGFBP-1 mRNA in dexamethasone-treated cells primarily reflected increased transcription rather than increased mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1990 Oct
PMID:Dexamethasone stimulates transcription of the insulin-like growth factor-binding protein-1 gene in H4-II-E rat hepatoma cells. 170 85

The liver is an epithelioid organ that can regenerate following partial hepatectomy. Although it is composed mainly of hepatocytes, it has a complex, multicellular architecture, implying that intercellular communications must exist during regeneration. As in other mitogen-stimulated cells, immediate-early growth response genes induced in the absence of prior protein synthesis are likely to play an important regulatory role in the regenerative process. Through differential screening of regenerating liver cDNA libraries, we found that one of the most highly expressed immediate-early genes in liver regeneration encodes the rat homolog of the low-molecular-weight insulinlike growth factor (IGF)-binding protein (IGFBP-1). This protein has been implicated in enhancing the mitogenic effect of IGF on tissues. IGFBP-1 gene induction is transcriptionally mediated and specific to regenerating liver, as the gene is not expressed in mitogen-stimulated fibroblasts. IGFBP-1 expression has been shown to increase under low-insulin conditions such as diabetes, and the complex regulation of expression is indicated by our finding that insulin treatment of H35 rat hepatoma cells, which induces proliferation, also causes a rapid decrease in transcription and expression of the IGFBP-1 gene. Of note, IGFBP-1 mRNA is abundant in fetal rat liver, implying that it participates in normal liver growth and development. Although regenerating liver cells continue to produce IGF-I, we did not detect IGF-I receptor mRNA during the first 24 h after hepatectomy. However, some IGFBPs may act to enhance the activity of IGF-I independently of IGF-I receptors. Thus, IGF-1 and IGFBPs may interact with hepatocytes or nonparenchymal liver cells, through either IGF-I or novel receptors. In this way, IGFBP-I and IGF-I could act in a paracrine and/or autocrine fashion in maintaining normal liver architecture during regeneration.
Mol Cell Biol 1991 Mar
PMID:The gene encoding rat insulinlike growth factor-binding protein 1 is rapidly and highly induced in regenerating liver. 170 4

The sensitivity of the alpha-fetoprotein (AFP) gene to digestion by the enzyme DNaseI, and the presence of hypersensitive sites in the 5' region of this gene, were examined in hepatoma x fibroblast hybrid cells that exhibit extinction of AFP gene expression. Major changes occur in the extinguished gene, i.e., loss of long-range sensitivity to DNase digestion and of the hypersensitive sites. In this respect, the extinguished gene resembles the corresponding silent gene present in fibroblasts, but differs from the silent gene present in normal adult hepatocytes. These observations suggest that extinguisher factors acting on the AFP gene alter its conformation.
Somat Cell Mol Genet 1991 Jan
PMID:Major chromatin changes accompany extinction of alpha-fetoprotein gene in hepatoma x fibroblast hybrids. 170 63

The capacity of a preS1-specific monoclonal antibody (McAb) F35.25 to block the attachment of preS1-specific ligands to human hepatoma HepG2 cells was studied. In order to define more precisely the fine epitope specificity of McAb F35.25, its reaction with synthetic peptides derived from the preS1 sequence (12-53) was investigated. McAb F35.25 was found to recognize better synthetic peptide preS(21-47) from the adw 2 and ayw sequences than the synthetic peptide preS(32-53) adw 2. The shortest sequence recognized by McAb F35.25 among the peptide sequence studied was preS(32-47). The corresponding amino acid sequence (for HBV subtype adw 2) is PAFGANSNNPDWDFNP. As expected, it was found that McAb F35.25 inhibited the attachment of HepG2 cells to HBsAg-cellulose, as well as to preS(21-47)-cellulose, corresponding to two HBV subtypes adw 2 and ayw. Finally, the inhibitory effect of different peptides on the interaction of McAb F35.25 with HBsAg particles containing the preS1 sequence was also studied. The peptide preS(12-47) appeared to be the most effective inhibitor. Therefore, the McAb F35.25 is specific for the sequence preS1(X to 47), where (12 less than or equal to X less than 32). These results indicate that McAb F35.25 is probably virus-neutralizing and represents a reagent of great value to study the interaction between HBV and hepatocytes independently of d/y subtype changes.
Mol Immunol
PMID:Inhibitory activity of monoclonal antibody F35.25 on the interaction between hepatocytes (HepG2 cells) and preS1-specific ligands. 171 75

LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations were observed, suggesting that ras activation is not involved in spontaneous hepatocarcinogenesis in LEC rats. The expression of mRNAs for c-myc, Ha-ras, c-raf, and the protein phosphatase 2A alpha gene (PP-2A alpha) was also examined in the four HCCs by northern blot analysis. Three of the four HCCs had c-myc expression levels approximately 30-fold higher than that in the liver of control Long-Evans rats with an agouti coat color (LEA), a sibling line of LEC rats, while the remaining HCC had an expression level sevenfold higher than that of control. In contrast, the expression levels of the Ha-ras, c-raf, and PP-2A alpha genes were the same as those in the livers of control rats. Studies of c-myc expression and mitotic index in five other HCCs, two hyperplastic nodules, and two nontumorous portions of livers of HCC-bearing LEC rats that had chronic-phase hepatitis suggested that the high level of c-myc gene expression was not due only to increased cell proliferation but might possibly be more integrally involved in hepatocarcinogenesis.
Mol Carcinog 1991
PMID:Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats. 171 40

Enhancer/promoter elements from two pancreas-specific genes, those encoding amylase and elastase, were ligated to the bacterial GPT gene. The resulting construct can be used to select for expression of gene products which activate these pancreas-specific promoters in hybrid cells. The selectable GPT construct was stably transferred into several cell lines either directly or by cotransfection with pSV2Neo. GPT was expressed when transferred to pancreatic cell lines but not when transferred to GPT-fibroblast (L) cells or hepatoma cells. When the transformed L cells and hepatoma cells were fused with pancreatic cell lines, GPT was activated in the hybrid cells. Endogenous pancreas-specific genes from the L-cell and hepatoma parents were also activated in the hybrids. In addition, a pancreas-specific nuclear protein, PTF1, was produced in pancreatic and hybrid cells, correlating with GPT expression. The transformed L cells and hepatoma cells thus contained a nonexpressed construct which could be activated in trans by factors present in pancreatic cells. The hepatoma hybrid also continued to produce albumin, demonstrating the coexpression of liver and pancreas-specific genes in the hybrid-cell population. Cell lines carrying the amylase/elastase/GPT construct may be useful as a selection system for cloning of pancreatic transcription activators.
Mol Cell Biol 1991 Sep
PMID:Transactivation of pancreas-specific gene sequences in somatic cell hybrids. 171 19

Transcription of the rat alpha 1-acid glycoprotein (AGP) gene is induced by glucocorticoids. In addition to the glucocorticoid response element which maps to bases -120 to -107, sequences located between bases -106 to -42 have been shown to be necessary for hormone induction. We have previously identified multiple sites of C/EBP interaction with the AGP promoter in the region -106 to -64. In this study, we purify and identify a C/EBP family member, AGP/EBP(LAP), present in the rat hepatoma cell line HTC (JZ.1) which also binds to the C/EBP recognition sites in this region. Mutations in the recognition sites that prevent binding are analyzed, and the results suggest a positive as well as a possible inhibitory role for AGP/EBP(LAP) in the glucocorticoid induction of the gene in HTC (JZ.1) cells.
Mol Cell Biol 1991 Oct
PMID:AGP/EBP(LAP) expressed in rat hepatoma cells interacts with multiple promoter sites and is necessary for maximal glucocorticoid induction of the rat alpha-1 acid glycoprotein gene. 171 23


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