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)

The angiotensinogen gene encodes the precursor protein for the potent vasoconstrictor angiotensin II. Although the gene is expressed in several tissues, the liver is the major source of circulating protein. In previous in-vivo studies we have found that a mini-gene containing 750 bp of 5'-flanking sequence is transcribed in a manner which largely parallels the expression of the endogenous gene. In this report, we characterized conserved elements in the promoter region, in order to determine their role in the transcription of the angiotensinogen gene. Constructs fused to the chloramphenicol acetyl transferase (CAT) reporter gene were transfected into hepatocarcinoma Hep G2 cells as well as into nonhepatic cell lines. We found that 5'-deletion mutant constructs, containing sequences from +25 to -90 bp and -321 to -750 bp, were each able to activate transcription. These constructs contain the TATA box and core promoter sequences, including an Sp1-binding site, and two glucocorticoid responsive elements respectively. In the non-hepatic cell lines, HeLa and Jeg-3, we found that the constructs were transcribed at a much lower rate when compared with the expression of a plasmid containing the Rous sarcoma virus long terminal repeat fused to the CAT gene. Constructs which included sequence 5' to -244 were oestrogen inducible. An element which is conserved between rodent and human angiotensinogen promoters is contained within a sequence which is oestrogen responsive, while another binds the liver-enriched transcriptional activator hepatocyte nuclear factor 1. However, the role of this transactivator in the transcription of angiotensinogen remains uncertain.
J Mol Endocrinol 1992 Aug
PMID:The function of conserved elements in the promoter of the mouse angiotensinogen gene. 151 23

Co-secretion of plasminogen activator inhibitor type 1 (PAI-1) and urokinase-type plasminogen activator was identified in short-term cultures of primary type II pneumocytes isolated from adult rats. After separation by sodium dodecyl sulfate (SDS)-PAGE and reverse fibrin autography (reverse FA) of serum-free conditioned medium (SFCM), cellular lysate, and extracellular matrix (ECM), the inhibitor was seen as a zone of spared lysis at an apparent molecular mass of 46 to 48 kD. The plasminogen activator (PA) activity could only be visualized when human instead of bovine fibrin was used in the indicator gel. It presented as a single band of lysis at an apparent molecular mass of 45 kD when tested by regular FA and was found adjacent to PAI-1 when examined by reverse FA. Immunoblot analysis of type II pneumocyte SFCM, cellular lysate, and ECM revealed two bands at 46 and 48 kD, consistent with the apparent molecular masses (Mr) reported for rat PAI-1 from HTC hepatoma cells. Type II pneumocyte PAI-1 formed SDS-resistant complexes with tissue-type and urokinase-type plasminogen activator and was found to be stable to acid, to short-term exposure to heat, and to the denaturants guanidine HCl and SDS, while being sensitive to treatment with alkali and urea. When levels of type II pneumocyte PAI-1 activity were monitored over time during short-term culture conditions, the level of PAI-1 in SFCM remained stable, whereas activity in the lysate accumulated and activity in the ECM declined.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1992 Feb
PMID:Plasminogen activator inhibitor type 1 production by rat type II pneumocytes in culture. 154 Mar 77

Angiotensinogen is the precursor molecule of one of the most potent vasoactive substances, angiotensin-II. Angiotensinogen is normally synthesized in the liver and secreted into the plasma where it is converted into angiotensin-II by the combined proteolytic action of renin and angiotensin converting enzyme. Angiotensinogen levels in the plasma are modulated by a number of pathological and physiological factors. In order to understand the regulation of angiotensinogen gene expression, we have constructed an expression vector in which 688 bp of the 5'-flanking region of the rat angiotensinogen gene were attached to the chloramphenicol acetyl transferase (CAT) coding sequence. We have also obtained 5'-sequential deletion mutants from the rat angiotensinogen promoter attached to the CAT gene, and have identified multiple cis-acting DNA sequences involved in the regulation of angiotensinogen gene expression by transient transfection of these recombinant DNA molecules in human hepatoma cell lines, Hep3B, and HepG2.
Cell Mol Biol 1992 Feb
PMID:Identification of cis-acting DNA elements involved in the regulation of angiotensinogen gene expression. 155 46

In a previous work on rat liver microsomes, we demonstrated that cytochrome P450 isozymes (P450) are engaged in the metabolism of RU486. In order to study the underlying mechanism at the molecular level, our investigations were shifted to a simplified system of cultured hepatoma cells which present a dissociation in the expression of distinct P450 coding genes. Our results show that Fao cells represent a convenient model to study both: (i) the degradation of RU486. Forms IIB1,2 and IIC7, which are present in Fao cells, may contribute to the demethylation of the molecule. Form IIIA, which has not been detected in Fao cells, is probably responsible for its oxidation in the liver; (ii) the effect of RU486 on the expression of P450 enzymes. Unlike other steroids (dexamethasone and pregnenolone 16 alpha-carbonitrile), RU486 does not induce P450 activity but inhibits the inducing activity of other agents such as dexamethasone and also phenobarbital. These findings may be important for the therapeutic use of RU486 since its inhibitory effect on P450 activity may be at the origin of drug interactions by modifying the endogenous hormonal status.
J Steroid Biochem Mol Biol 1992 Mar
PMID:How the potency of the steroid RU486 is related to P450 activities induced by dexamethasone and phenobarbital in rat hepatoma cells. 156 37

The metabolism of dihydrotachysterol (DHT), a hydrogenated analogue of vitamin D, has been studied in vivo using man and rat and in vitro using the perfused rat kidney, and hepatoma (3B) and osteosarcoma (UMR-106) cell lines. In vivo a large number of metabolites appeared in the plasma of rats given DHT2 and DHT3. Of particular interest was a compound more polar than 25-hydroxy-DHT, which has been designated compound H. Further study of this compound showed that it was composed of two components, one (Ha) being in much lower concentration than the other (Hb). The production of T2/H (peak H from DHT2) was demonstrated in human plasma after administration of oral DHT2. Comparison of the metabolites formed in vivo with those isolated from the rat kidney perfused with 25-hydroxy-DHT3 in vitro showed that 25-hydroxy-DHT3 was metabolized along two metabolic pathways previously described for vitamin D, culminating in the production of 25-hydroxy-DHT3-23,26-lactone and 23,25-dihydroxy-24-oxo-DHT3. The osteosarcoma cell line metabolized 25-OH-DHT3 in vitro along the same two metabolic pathways already demonstrated in the perfused rat kidney. More polar metabolites than compound H seen in rat plasma in vivo were shown to be metabolites of compound H and similar metabolites were also produced in the osteosarcoma cell line from chemically synthesized 1 alpha,25-dihydroxy-DHT3. The hepatoma cell line 25-hydroxylated DHT and no feed-back inhibition was observed. Use of the hepatoma cell to 25-hydroxylate a number of chemically synthesized 1-hydroxy-DHTs indicated that compound Ha was indistinguishable from 1 alpha,25-dihydroxy-DHT whereas compound Hb is possibly 1 beta,25-dihydroxy-DHT. Studies with the VDR in both chick gut and calf thymus indicated that 1 alpha,25-dihydroxy-DHT is very effective in displacing radiolabelled 1 alpha,25-dihydroxyvitamin-D3 and is thus most likely to be the calcaemic metabolite of DHT.
J Steroid Biochem Mol Biol 1992 Mar
PMID:The metabolism of dihydrotachysterols: renal side chain and non-renal nuclear hydroxylations in vivo and in vitro. 156 63

A major regulatory element required for expression of the human alpha-globin genes is located 40 kb upstream of the embryonic zeta-globin gene. To understand how this and other locus control region (LCR) elements contribute to high-level expression in erythroid cells, we have performed high-resolution, in vivo dimethyl sulfate footprinting. In addition, we have modified the dimethyl sulfate-based ligation-mediated polymerase chain reaction in vivo footprinting procedure to permit the assessment of interactions at guanine and adenine residues, rather than guanines alone. In vivo footprinting of the human alpha-LCR element carried on chromosome 16 in a mouse erythroleukemia cell environment revealed protein occupancy at GATA-1, AP-1/NF-E2, and CACC/GGTGG motifs, specific differences compared with in vitro protein binding, and distinct changes in one region upon dimethyl sulfoxide-induced cellular maturation. No protein contacts were detected in nonexpressing hepatoma cells. In addition, we have demonstrated that two AP-1 motifs in the alpha-LCR element which are occupied in vivo bind purified mouse NF-E2 protein in vitro. Our data suggest that three proteins, GATA-1, NF-E2, and unknown CACC/GGTGG factors, are minimally required as DNA-binding proteins for the function of LCR-like elements. The juxtaposition and interaction of these factors with each other, and with accessory proteins not directly in contact with DNA, are likely to account for the relative position independence of the upstream globin regulatory elements.
Mol Cell Biol 1992 May
PMID:In vivo footprinting of the human alpha-globin locus upstream regulatory element by guanine and adenine ligation-mediated polymerase chain reaction. 156 44

Variations in the biological activity of antisteroids, as determined by their percent agonist activity, is a well known but poorly understood phenomenon. For example, in tyrosine aminotransferase (TAT) induction by the antiglucocorticoid dexamethasone 21-mesylate in rat hepatoma tissue culture cells, the percent agonist activity varies with the density of cultured cells. A 21-basepair sequence of the rat TAT gene has now been isolated which confers all of the induction properties of the endogenous TAT gene to homologous and heterologous promoters and genes. We call this 21-basepair sequence, which acts in concert with a trans-acting factor identified by gel shift experiments, a glucocorticoid modulatory element. The changes in induction properties were found to be independent of the fold induction by dexamethasone, thus arguing that the GME does not synergize with the glucocorticoid response element. A model incorporating this new element is advanced which can explain the observed variations of TAT induction and may be generally applicable for the mechanism of action of other steroid hormones.
Mol Endocrinol 1992 Mar
PMID:Modulation of transcription factor activity by a distant steroid modulatory element. 158 17

For an understanding of the molecular basis of the marked decrease in catalase activity of various tumor cells, expression of the catalase gene was studied in rat and human hepatoma cell lines and in rat liver, which was used as a control with high activity. RNA blot hybridization profiles and run-on assays indicated that the decrease in catalase activity was due to depression of catalase gene transcription. Chloramphenicol acetyltransferase (CAT) assays for the fragments with various lengths of the 5'-flanking region (up to -4.5 kb from the ATG codon) of the catalase gene revealed the presence of several cis-acting elements involved in the negative regulation of transcription. The most-upstream element with the strongest activity (-3504 to -3364 bp), when linked to the catalase promoter region (-126 bp) of the CAT construct and subjected to an in vitro transcription assay, did not yield transcripts in experiments with the hepatoma nuclear extract, whereas the unlinked template did yield transcripts. A gel shift competition assay using hepatoma nuclear extract showed the core sequence of the silencer element to be 5'-TGGGGGGAG-3'. A homology search found that the same core sequence was also present in 5'-flanking regions of the albumin gene and of some other liver enzyme genes, the expression of which has been reported to be down regulated in some hepatoma cells. Southwestern (DNA-protein) analysis demonstrated that an approximately 35-kDa nuclear protein bound to the silencer element was present in hepatoma cells but not in rat liver cells.
Mol Cell Biol 1992 Jun
PMID:Negative regulation of catalase gene expression in hepatoma cells. 158 55

We have cloned full-length DDC cDNAs from a human hepatoma cDNA library [DDC; dopa decarboxylase; aromatic-L-amino acid decarboxylase, EC 4.1.1.28]. The protein encoded by hepatoma cells is the same as that encoded by adrenal chromaffin derived pheochromocytoma cells, despite reported differences in biochemical properties. We have confirmed the location of the DDC gene to chromosome 7 using a new panel of somatic cell hybrids, and we have localized the gene to band p11 on chromosome 7 by fluorescent in situ hybridization. The human gene retains 65% amino acid identity with Drosophila DDC (Accession No. X04426) and considerable structural similarity with other enzymes (F.R. Jackson, 1990, J. Mol. Evol. 31:325-329, and references therein).
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PMID:Human dopa decarboxylase: localization to human chromosome 7p11 and characterization of hepatic cDNAs. 161 8

Alterations in lipid content and composition in the N-nitrosodiethylamine-induced hepatocarcinoma were investigated. Rats were administered with N-nitrosodiethylamine in the drinking water for 12 weeks followed by normal tap water for another 6 weeks. The cholesterol content in the liver was increased shortly after the administration of N-nitrosodiethylamine and remained elevated after the removal of the nitrosoamine from the water. The phosphatidylethanolamine level was elevated during N-nitrosodiethylamine administration with a concomitant reduction in phosphatidylcholine level. Lysophosphatidylcholine and sphingomyelin levels were increased during the last four weeks of the study. The level of phosphatidylinositol was substantially reduced after eight weeks of N-nitrosodiethylamine treatment, and remained low during the post-treatment period. We postulate that changes in lysophosphatidylcholine and sphingomyelin may be a compensatory mechanism for maintaining the asymmetrical distribution of choline-containing lipids in the outer leaflet of the membrane. The elevated level of cholesterol may be a useful indicator for the early detection of N-nitrosodiethylamine-induced hepatocarcinoma.
Mol Cell Biochem 1992 Jan 15
PMID:Changes in lipid content and composition during the development of N-nitrosodiethylamine induced hepatocarcinoma. 161 22


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