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)

A fraction containing liver- and hepatoma-specific non-histone proteins has been isolated from the chromatin of mice. Amino acid analysis of this fraction shows that it contains 16 mol of glutamic acid, 10 mol aspartic acid, 7 mol of both arginine and lysine per 100 mol and contains no cysteine or tyrosine. The proteins in this fraction are strongly associated with DNA and are co-extracted with histones from chromatin with 0.25 M HCl. In chromatin from age-related hepatomas, the amount of this fraction increased six-fold. This increase in concentrations of these chromatin proteins may be associated with changes of chromatin structure necessary to initiate malignant growth in liver cells.
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PMID:The characterization of non-histone proteins whose amounts increase in chromatin from mouse hepatocarcinomas. 711 99

A protein showing lower electrophoretic mobility in acidic urea polyacrylamide gels than did the usual histone H1 subfractions has been detected among the H1 histones extracted from chromatin of a transplantable hamster hepatoma, originally induced by Kirkman and Robbins. It was proved to be a true H1 histone subfraction. It differs from the remaining ones by the total chain length, amino acid composition, and isoelectric point value. It is not a phosphorylated or phosphoribosylated metabolic form of another subfraction. Its proteolytic degradation products (obtained by thrombin and trypsin digestion) closely resembled those obtained from other H1 subfractions. The investigated hepatoma seems to provide an interesting model of neoplastic cells showing a distinct difference in histone composition from the homologous normal tissue.
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PMID:A low-electrophoretic-mobility H1 histone subfraction from Kirkman-Robbins hamster hepatoma. 723 41

Electrophoretically slow H1 histone subfractions with mobilities identical to that of the subfraction found in the Kirkman-Robbins hamster hepatoma chromatin have been shown to be present in 12-day hamster embryos and in a sarcoma-type hamster tumor induced by SV40. No subfractions of such mobility were found in hamster liver, regenerating liver, thymus, spleen, and a fast-growing transplantable amelanotic hamster melanoma. A suggestion is made that some defective mechanisms of differentiation may affect the regulation of expression of the genes coding for the H1 histone subfractions. The same mechanisms may possibly but not necessarily be connected with the molecular events leading to neoplastic growth.
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PMID:Occurrence of the low-mobility H1 histones subfraction in embryonic, differentiated, and neoplastic tissues of the Syrian hamster. 723 42

The phosphorylation of endogenous membrane proteins by an endogenous protein kinase was studied in isolated plasma membranes from AH-66 hepatoma ascites cells using [gamma-32P]ATP as a precursor. The phosphorylation occurred very rapidly in the presence of 10 mM Mg2+ and reached a maximal level at 2 min. Ca2+ strongly inhibited the phosphorylation reaction and antagonized the activation produced by Mg2+. Neither cyclic AMP nor cyclic GMP had a significant effect on the phosphorylation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography showed that only membrane proteins ranging in molecular weight from 125,000 to 200,000 were heavily phosphorylated and those of less than 60,000 molecular weight were not phosphorylated at all. The protein kinase activity was readily extractable from the plasma membranes with 1 mM EDTA at pH 8.5. Among exogenous substrates, the extracted protein kinase catalyzed the phosphorylation of histone, protamine and phosvitin rather than casein. When the extracted protein kinase was subjected to chromatography on DEAE-Sepharose, a single major peak of cyclic AMP-independent protein kinase was eluted at a position quite different from those of the cytosolic protein kinases.
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PMID:Endogenous protein phosphorylation in isolated plasma membranes of AH-66 hepatoma ascites cells. 728 78

We have utilized sodium butyrate to inhibit histone deacetylases in order to study the rates of histone acetylation in hepatoma tissue culture cells. In this manner, we have been able to observe two rates of hypermodification of acetylated core histone. By selectively radolabeling acetylated histone fractions based upon differences in their acetate exchange rates, we have identified the rate of histone acetate hydrolysis and the rate of hyperacetylation in 50 mM sodium butyrate for two distinct populations of acetylated histone. One population, comprising no more than 15% of each of the non-H1 histones, is characterized by rapid hyperacetylation (t 1/2 congruent to 7 min for monoacetylated H4) and the rapid (t 1/2 congruent to 3 to 7 min) removal of this modification. A second population is deacetylated with t 1/2 congruent to 30 min and is hypermodified much less vigorously in 50 mM sodium butyrate (t 1/2 congruent 200 to 300 min for monoacetylated H4). Unlike the rapidly metabolized group, the fraction of total histone in this slow population varies between the four core histones. In addition, there appears to be no interconversion of histone between these populations.
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PMID:The identification of distinct populations of acetylated histone. 741 Apr 15

It has been previously shown that micrococcal nuclease digestion and subsequent fractionation of hen oviduct nuclei generates fractions enriched (first supernatant fraction - 1SF) and depleted (second supernatant fraction - 2SF) in ovalbumin genes, while a third fraction, the pellet fraction, contains about the same level of this gene as whole chromatin (Bloom and Anderson (1978) Cell 15, 141-150). We have utilized this fractionation method in an attempt to assess the extent and kinetics of histone acetylation associated with chromatin from the 1SF, 2SF, and pellet fraction. Hepatoma Tissue Culture (HTC) cells were labelled for 30 minutes in vivo with 3H-acetate, nuclei isolated and the chromatin fractionated. The specific activity of the histones in the 1SF was slightly greater than that of the 2SF (1.2 to 1.6 fold difference) independent of the length of nuclease digestion. If the labelling period is followed by short (10 to 60 minute) treatment of the cells with sodium butyrate, the more rapidly as well as more extensively acetylated histones are also preferentially found in the 1SF. This is in part the result of segregation of chromatin particles into the 1SF as the histones associated with these particles become hyperacetylated. That is, the extent of histone acetylation regulates the distribution of chromatin in the 1SF, 2SF and pellet fraction.
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PMID:Segregation of rapidly acetylated histones into a chromatin fraction released from intact nuclei by the action of micrococcal nuclease. 743 28

An important role in the control of gene expression has been attributed to phosphoproteins present among chromatin non-histone proteins. In a previous work we have shown that at least part of these phosphoproteins are associated with nucleosomes. In this work we wanted to establish whether this association occurs with all nucleosomes or with the nucleosomes present in fragments preferentially released by a mild micrococcal nuclease digestion, which originated essentially from active parts of chromatin. Phosphoproteins were labelled in vivo by incubating hepatoma tissue-cultured cells with [32P]phosphate and chromatin was submitted to a limited micrococcal nuclease digestion. The released fragments were fractionated by preparative gel electrophoresis. [32P]Phosphoproteins were essentialy found in the smallest released fragments: monomers and dimers of nucleosomes. The same result was obtained when the phosphoproteins were labelled in vitro by incubating each fragment obtained by the preparative electrophoresis in the presence of [gamma-32P]ATP. It indicates that part of the protein kinase activity was strongly bound to the particles. The bound phosphoproteins were analysed by sodium dodecylsulfate/polyacrylamide gel electrophoresis. Two main polypeptides were characterized: phosphopeptide a, Mr 41000, present in all small fragments; phosphopeptide b, Mr 31000, present in all small fragments, except in the fastest moving nucleosomes. Phosvitin kinase was found associated with the small released fragments, its specific activity was by far the highest in the fraction which includes the dimers of nucleosomes. It is concluded that phosphoproteins and protein kinases are associated with the nucleosomes of the active parts of chromatin, which suggests a role of these proteins in the control of gene expression.
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PMID:Localization of phosphoproteins and of protein kinases in chromatin from hepatoma tissue-cultured cells. 743 87

We have studied the pattern of histone acetylation in intact rat hepatoma tissue culture (HTC) cells, in isolated HTC nuclei, and in chromatin prepared from these cells. The results have been compared with the histone acetylation observed in a reconstituted in vitro system consisting of a variety of purified soluble nucleosomal substrates, [3H]acetyl-CoA, and one of two different purified histone N-acetyltransferases. Acetylase A, a highly purified nuclear enzyme, catalyzed the acetylation of 1) nucleosomally bound histones in the order H4 > H2a = H2b > H3, and 2) free histones in the order H4 > H3 > H2b > H2a. Acetylase B, a cytoplasmic enzyme, modified only free histone H4, and it failed to acetylate histones in nucleosomes. The pattern of histone acetylation obtained by in vitro reaction of purified nucleosomes with the purified nuclear acetylase A differed considerably from the corresponding patterns obtained either by acetate labeling of intact cells, or by the acetyl-CoA labeling of nuclei and crude preparations of nucleosomes, as catalyzed by endogenous chromatin-bound acetylase(s). The most striking difference was in the relative preference for acetylation of histone H4 versus acetylation of histone H3: with the purified acetylase, histone H4 in nucleosomes was acetylated to a much greater extent than was histone H3, whereas the reverse preference was found with the endogenous acetylase(s). This result suggests that either a second nuclear acetylase enzyme, or a separate cofactor for acetylase A, is required for histone H3 acetylation in vivo. In support of this view, we find that the acetylation of histones H4, H2a, and H2b in nuclei is inhibited by urea, salt, or N-ethylmaleimide treatments to a very different extent than is the acetylation of histone H3. By comparing n-butyrate-treated HTC cells with untreated cells, classes of nucleosomes specially accessible and inaccessible to acetylation can be distinguished (Cousens, L. S., Gallwitz, D., and Alberts, B. M. (1979) J. Biol. Chem. 254, 1716-1723). Both types of special nucleosomal reactivities were present in isolated nuclei, but were lost as nucleosomes were purified from these cells. OUr data thus suggest the existence of labile specificity factors or structures, which guide the acetylase(s) to restricted groups of otherwise similar nucleosomes in vivo.
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PMID:Comparative studies of histone acetylation in nucleosomes, nuclei, and intact cells. Evidence for special factors which modify acetylase action. 744 May 48

The effects of ultraviolet C (UVC) irradiation on nucleosome assembly and its stability were investigated quantitatively using an in vitro nucleosome assembly system comprising a plasmid DNA of pBR322 and core histones isolated from rat ascites hepatoma cells. Nucleosomal formation was estimated by analyzing the resulting DNA supercoils. When UVC-irradiated (3000 J/m2) DNA was used as a substrate for the nucleosome assembly system, the nucleosomal formation efficiency was reduced by half compared with nonirradiated DNA. On the other hand, when the reconstituted nucleosomes (minichromosomes) on the nonirradiated DNA were irradiated with UVC (3000 J/m2), about half each were disrupted and retained. These results indicate that it is difficult for UV-damaged DNA regions to supercoil around the histone octamers to form nucleosomes and that the histone octamers in the UV-damaged nucleosomes tend to be dissociated from DNA.
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PMID:The effects of ultraviolet C on in vitro nucleosome assembly and stability. 793 9

To develop a model for studies of liver growth control, we characterized cell cycle synchronization of liver-derived cells with sodium butyrate. Exposure of cultured HTC (rat hepatoma) cells to 5 mM butyrate arrested cell growth in a reversible manner. Flow cytometric analysis revealed that butyrate-treated HTC cells were restricted in G0/G1, as well as S/G2M phases. After release from butyrate arrest, HTC cells underwent synchronous cycles of DNA synthesis and transited through S phase. Inhibition of cell growth by butyrate was associated with a complex pattern of cell cycle regulated gene expression, including a decoupling of c-fos and c-jun gene expression. Transcription of c-fos, as well as c-jun increased with butyrate arrest, whereas steady rate mRNA levels of c-jun only were increased, suggesting additional regulation of c-fos. In addition, butyrate-arrested cells exhibited a transcriptionally determined accumulation of H3 histone, C-Ha-ras and ornithine decarboxylase mRNAs, suggesting that cell cycle-related check points following the onset of S phase were modulated. An increase in c-myc mRNA levels in butyrate-arrested cells was post-transcriptionally regulated. After release from butyrate-arrest, the abundance of immediate early, as well as S phase regulated, gene expression changed coordinately with S phase cell transitions. Thus, exposure of HTC cells to butyrate modulates cell cycle regulated gene expression, inhibits cycling, and results in accumulation of cells in specific compartments. Synchronization of liver cells with butyrate should, therefore, provide a useful model for defining cell cycle-related events in response to various mitogenic stimuli.
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PMID:Butyrate synchronization of hepatocytes: modulation of cycling and cell cycle regulated gene expression. 794 6


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