Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We searched for a new cell aggregation factor for hepatoma AH109A cells, and found one we called HAF in the culture filtrate of Streptomyces sp. strain No. A-6143 isolated from a soil sample. HAF was purified by salting-out with ammonium sulfate. DEAE-cellulose column chromatography, gel filtration on Sephadex G-100, and hydroxylapatite column chromatography, HAF was glycoprotein which had a molecular weight of about 73,000. HAF was stable from pH 6 to 8 at 37 degrees C and up to 40 degrees C at pH 8.0 and the aggregation activity of HAF was maximum around pH 8 at 30 degrees C. The activity was not influenced by some saccharides, but it was inhibited by EDTA and EGTA: moreover HAF activity was restored by the addition of calcium ions. HAF aggregated hepatoma AH136B and COS-7 cells as well as hepatoma AH109A cells, but it was inert to other cancer cells and human erythrocytes. These properties proved that HAF is completely different from other aggregation factors for cancer cells so far reported.
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PMID:HAF, hepatoma aggregation factor produced by Streptomyces sp. strain No. A-6143. 136 99

The immunosuppressant rapamycin inhibited proliferation of the H4IIEC hepatoma cell line. Rapamycin, but not its structural analog FK506, also inhibited the basal and insulin-stimulated activity of the p70 ribosomal protein S6 kinase. By contrast, insulin stimulation of the p85 Rsk S6 kinase and mitogen-activated protein (MAP) kinase activity were unaffected by drug. Rapamycin treatment of COS cells transfected with recombinant p70 S6 kinase completely inhibited the appearance of the hyperphosphorylated form of p70 S6 kinase concomitant with the inhibition of enzyme activity toward 40S subunits. Thus, rapamycin inhibits a signal transduction element that is necessary for the activation of p70 S6 kinase and mitogenesis but unnecessary for activation of p85 Rsk S6 kinase or MAP kinase.
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PMID:Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase. 138 Jan 82

The elongated mutant of alpha 2-plasmin inhibitor (alpha 2 PI) designated as alpha 2 PI-Nara is caused by a frameshift mutation found near the 3' end of the coding region of the alpha 2 PI gene. To elucidate the mechanism by which this molecular abnormality leads to alpha 2 PI deficiency in plasma, we transfected an expression plasmid for alpha 2 PI-Nara into a monkey kidney cell line COS-7 or human hepatoma cell line HepG2 synthesizing alpha 2 PI, and analyzed the secretory process of the expressed alpha 2 PI-Nara by radioimmunoprecipitation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. The results obtained showed that the recombinant alpha 2 PI-Nara was retained within the cells for prolonged periods as an endoglycosidase H-sensitive precursor form, and only a small portion of the recombinant protein was secreted into the medium as a neuraminidase-sensitive mature form. These results suggest that instead of being secreted from the cells, most of the alpha 2 PI-Nara undergoes degradation within the cells while its transport is retarded in the intracellular secretory pathway; thus, alpha 2 PI-Nara should lead to the alpha 2 PI deficiency primarily by causing a block in the intracellular transport from the endoplasmic reticulum to the Golgi complex.
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PMID:Impaired secretion of mutant alpha 2-plasmin inhibitor (alpha 2 PI-Nara) from COS-7 and HepG2 cells: molecular and cellular basis for hereditary deficiency of alpha 2-plasmin inhibitor. 168 97

Human apolipoprotein H (ApoH), also called beta 2-glycoprotein I, is a 50-kDa serum glycoprotein whose function is not clearly defined. We have cloned and sequenced ApoH cDNAs both from human liver and from a human hepatoma cell line (HepG2). Both cDNA sequences predict a protein 345 amino acids (aa) in length. This sequence includes a 19-aa hydrophobic, N-terminal signal sequence which is not present in the mature protein [Lozier et al., Proc. Natl. Acad. Sci. USA 81 (1984) 3640-3644]. It differs from this previously reported aa sequence at two positions, both of which strengthen the conservation among the four short consensus repeats within the ApoH molecule. COS-1 cells transiently transfected with the ApoH cDNA in a eukaryotic expression vector produced a single species of ApoH mRNA and secreted in the ApoH protein. The level of ApoH mRNA expressed by HepG2 cells is downregulated by incubation with inflammatory mediators, implying that ApoH is a negative acute-phase protein.
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PMID:Nucleotide sequence and expression of the human gene encoding apolipoprotein H (beta 2-glycoprotein I). 174 14

Two types of partial cDNAs encoding human acid sphingomyelinase (EC 3.1.4.12; ASM) were recently isolated from fibroblast and placental cDNA libraries (Quintern, L. E., Schuchman, E.H., Levran, O., Suchi. M., Ferlinz, K., Reinke, H., Sandhoff, K., and Desnick, R. J. (1989) EMBO J. 8, 2469-2473). The cDNA inserts had identical sequences with the exception of an internal region; type 1 cDNAs (representing approximately 90% of the ASM cDNAs isolated) had 172 in-frame base pairs (bp), which were replaced in the type 2 cDNAs by a 40-bp in-frame sequence. Northern hybridization and RNase protection studies indicated that both type 1 and 2 transcripts were approximately 2.5 kilobases; therefore, efforts were directed to isolate full-length type 1 and 2 cDNAs by screening human placental, testis, hepatoma, and retinal cDNA libraries. In addition to type 1 and 2 cDNAs, a new type of ASM cDNA (type 3), which did not contain the type 1- or 2-specific regions, was isolated and sequenced. The full-length type 1 and the reconstructed full-length type 2 and 3 cDNAs were transiently expressed in COS-1 cells. Only the full-length type 1 transcript encoded catalytically active human ASM, demonstrating its functional integrity. The 2347-bp full-length type 1 placental cDNA (pASM-1FL) had an 87-bp 5'-untranslated region, an 1890-bp open reading frame encoding 629 amino acids, and a 370-bp 3'-untranslated sequence. The predicted location of the signal peptide cleavage site was after alanine 46. Two base differences were identified in codons 322 and 506 and shown to be polymorphisms with the common alleles having frequencies of 0.6 and 0.7, respectively. To determine the genomic organization of the type 1, 2, and 3 sequences, a 1665-bp genomic region containing both the unique type 1 (172 bp) and type 2 (40 bp) sequences was amplified by the polymerase chain reaction and sequenced. The 172-bp sequence was exonic, flanked by 5'- and 3'-intronic sequences of 1052 and 229 bp, respectively. The 40-bp type 2 sequence was intronic, occurring at the 5' end of the 1052-bp intron due to the use of a cryptic 5' donor splice site, which deleted the entire 172-bp exon and both flanking intronic sequences. The type 3 cDNA resulted from an alternative splicing event, which excised the 172-bp exon. These studies demonstrate the occurrence of alternatively splicing of the ASM transcript, but the existence of only one functional mRNA.
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PMID:Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs. 184 Jun

A full-length cDNA for the rat liver enzyme tyrosine aminotransferase has been used to construct mammalian expression vectors by recombinant DNA techniques. These vectors, which have employed either a simian virus 40 or a Rous sarcoma virus promoter, were transfected into a variety of nonhepatic mammalian cell lines in culture. Transient expression of tyrosine aminotransferase was readily observed after transfection into monkey COS cells and mouse L cells. Stable clones that express cloned tyrosine aminotransferase have been isolated from mouse L cells, hamster Wg1a fibroblasts, and Chinese hamster ovary (CHO) cells. A vector capable of expressing both tyrosine aminotransferase and dihydrofolate reductase was stimulated to undergo amplification by treatment with methotrexate in a CHO cell line deficient in the latter enzyme. Levels of tyrosine aminotransferase as much as 50-fold higher than typically seen in glucocorticoid-induced hepatoma cells were achieved in some CHO clones by this technique. The tyrosine aminotransferase produced at these highly amplified levels appeared structurally normal and had no major harmful effects on the cells.
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PMID:Expression and amplification of cloned rat liver tyrosine aminotransferase in nonhepatic cells. 196 11

A cDNA coding for an allelic variant of rat IID1, designated IID1v, was isolated that produced a P-450 having a 10-fold lower catalytic activity toward the substrate bufuralol when expressed in COS-1 cells (Matsunaga, E., Zanger, U. M., Hardwick, J. P., Gelboin, H. V., Meyer, U. A., and Gonzalez, F. J. (1989) Biochemistry, 28, 7349-7355). IID1 and IID1v cDNA-deduced proteins differed in sequence by 4 amino acid residues. IID1 has Val, Phe, Arg, and Leu while IID1v has Ile, Leu, Gln, and Phe at amino acid positions 123, 124, 173, and 380, respectively. Chimeric cDNAs between IID1 and IID1v were constructed and expressed in hepatoma cells using vaccinia virus. A chimera having the Phe (IID1v) at amino acid 380, with the remaining 3 variant amino acid residues of IID1, was found to have a 17-fold decrease in Vmax and a 2 to 3-fold decrease in Km for (+)-bufuralol 1'-hydroxylation when compared to a converse chimera having Ile (IID1) in a background of IID1v sequence. Although this enzyme lacked significant bufuralol metabolism, it was able to carry out debrisoquine 4-hydroxylation. In contrast, the chimera having Ile (IID1) at position 380 was lacking in debrisoquine 4-hydroxylation. Type I difference spectra analysis revealed that both forms could bind debrisoquine with similar spectral dissociation constants. These data demonstrate that the single amino acid substitution Ile380----Phe differentially decreases the catalytic activity of IID1 toward bufuralol but not debrisoquine.
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PMID:Sequence requirements for cytochrome P-450IID1 catalytic activity. A single amino acid change (Ile380 Phe) specifically decreases Vmax of the enzyme for bufuralol but not debrisoquine hydroxylation. 197 28

Three forms of basic fibroblast growth factor (bFGF), initiated at an AUG (18 kDa) and two CUG (21 and 22.5 kDa) start codons, were produced following transfection of COS cells with human hepatoma bFGF cDNA. The subcellular localization of the different forms was investigated directly or by using chimeric genes constructed by fusion of the bFGF and chloramphenicol acetyltransferase open reading frames. The AUG-initiated proteins were cytoplasmic, while the CUG-initiated forms were nuclear. The signal sequence responsible for the nuclear localization of bFGF is contained within 37 amino acid residues between the second CUG and the AUG start codons. Alternative initiation of translation regulates the subcellular localization of bFGF and thus could modulate its role in cell growth and differentiation control.
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PMID:Alternative initiation of translation determines cytoplasmic or nuclear localization of basic fibroblast growth factor. 198 49

Glucocorticoid regulation of rat growth hormone (rGH) gene expression has been investigated in a series of gene transfer studies into cells in culture. It has been established that sequences (-12 to -523) immediately flanking the start site for rGH gene transcription behave as a functional glucocorticoid inducible enhancer when associated with a heterologous promoter (RSV), displaying independence of orientation and position in mediating the glucocorticoid effect. The induction of chloramphenicol acetyl transferase (CAT) gene expression in these constructs by dexamethasone was established at the enzyme and mRNA levels and was inhibited in the presence of the antiglucocorticoid, RU 38486. The glucocorticoid inducible enhancer activity was not restricted to pituitary cells. The constructs containing the rGH-5'-flanking sequences, associated with the RSV promoter, also mediated glucocorticoid induction of CAT gene expression when transiently transfected into MH1C1 cells, a hepatoma cell line. The effect was similarly demonstrable on co-transfection of these constructs with a glucocorticoid receptor expression vector into receptor deficient COS cells. Two elements within these rGH sequences (-97 to -111 and -250 to -264) display partial homology with a consensus sequence computed for a group of glucocorticoid regulatory elements. Mutation of both of these elements or of the more proximal element alone (-97/-111) led to a complete loss of ability to mediate glucocorticoid induction of gene expression. However, the rGH sequences still mediated glucocorticoid induction of gene expression when the distal GRE-like element was mutated or deleted. Thus, the proximal rGH GRE-like element is absolutely required to mediate this glucocorticoid inducible enhancer activity.
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PMID:Functional glucocorticoid inducible enhancer activity in the 5'-flanking sequences of the rat growth hormone gene. 199 16

A 6.86 kb rat genomic DNA fragment containing the testis-specific histone H1t gene and the histone H4t gene has been sequenced. S1-nuclease protection analyses of total cellular RNA from rat liver and testis showed that histone H1t mRNA was present only in testis. Examination of various highly enriched populations of rat testis cell types revealed that H1t mRNA was found exclusively in a fraction enriched in pachytene spermatocytes. When protein, DNA interactions within the proximal promoter region of the histone H1t gene were examined by electrophoretic mobility shift assays, only minor differences were found in mobility shift patterns of the H1t promoter in assays comparing binding of nuclear proteins from pachytene spermatocytes and early spermatids. However, major differences in binding were observed upon comparing nuclear proteins from rat pachytene spermatocytes to liver. Comparison of binding patterns of rat testis, rat hepatoma H4 cells, HeLa cells, and COS-1 cells also revealed dramatic differences. Transcriptional activity of the histone H1t promoter was examined by measuring H1t promoted chloramphenicol acetyltransferase (CAT) mRNA levels in transient expression assays in transfected rat hepatoma H4 cells, HeLa cells, and COS-1 cells. These assays revealed that the histone H1t promoted CAT gene functioned poorly in HeLa cells and COS-1 cells compared to expression with the parent SV40 promoted vector pSV2CAT. The H1t promoted CAT gene apparently did not work at all in transfected rat hepatoma H4 cells, which is consistent with testis germinal cell specific expression of the histone H1t gene.
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PMID:Structural and functional analysis of the rat testis-specific histone H1t gene. 213 96


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