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)

Somatic cell hybrids between hepatoma and Friend erythroleukemia parental cells were studied for the expression of liver-specific and erythroid properties. Several independent clones were isolated using HAT selection and were shown to be true hybrids by isozyme and chromosome analysis. All displayed a complete extinction of hemoglobin and globin mRNA production, but a retention of albumin and transferrin secretion. The data suggest that erythroid differntiation is being actively inhibited by the hepatoma genome. Possible mechanisms that might explain these results are discussed in the light of current hypotheses regarding the mechanism of cell differentiation.
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PMID:Somatic cell hybrids between Friend erythroleukemia cells and mouse hepatoma cells. 20 66

Friend mouse erythroleukemia cells do not synthesize detectable levels of phenylalanine hydroxylase [phenylalanine 4-monooxygenase; L-phenylalanine, tetrahydropteridine:oxygen oxidoreductase (4-hydroxylating), EC 1.14.16.1] and hence are unable to grow in medium totally lacking tyrosine. These cells were fused with the cytoplasts of rat hepatoma cells that synthesize phenylalanine hydroxylase constitutively. Cytoplasmic hybrids [cybrids, Bunn, C. L., Douglas, C. W. & Eisenstadt, J. M. (1974) Proc. Natl. Acad. Sci. USA 71, 1681--1685] were selecte in medium without tyrosine. Cybrid clones expressed phenylalanine hydroxylase enzyme, which was of mouse type as determined by immunotitration and isoelectric focusing. This phenotype has been mainta ined even in the absence of any selective pressure. In contrast, in whole cell hybrids derived between the same parents, the expression of the phenylalanine hydroxylase gene was totally extinguished. One interpretation of these results is that the cytoplasm of rat hepatoma cells contain a positively acting factor(s) for the phenylalanine hydroxylase gene that brings about the activation of this gene in erythroleukemia cells.
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PMID:Epigenetic activation of phenylalanine hydroxylase in mouse erythroleukemia cells by the cytoplast of rat hepatoma cells. 29 Oct 52

Immunization of rabbits with rat leukemia DBLA-6 resulted in the production of antisera which upon absorption with hepatoma cells were specific for rat immature T lymphocytes. The antisera showed cytotoxicity against thymocytes and killed 75 approximately 90% of them, whereas the antisera had no cytotoxic effect on peripheral lymphocytes from the spleen, lymph node, and bone marrow of rats. The antisera also showed cytotoxicity against rat lymphatic leukemia and lymphoma cells of all lines tested but not against rat myelogenous leukemia and erythroleukemia cells. The cytotoxic activity of anti-DBLA-6 serum was completely absorbed with rat brain or thymocytes.
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PMID:Heterologous antiserum to a subpopulation of thymocytes and lymphomas in rats. 31 55

In vitro studies of the mouse erythroleukemia cell system have identified at least 300 agents capable of inducing differentiation by mechanisms that remain to be elucidated. We have recently begun to examine recombinant cytokines as possible agents in inducing differentiation of tumor cells, specifically, malignant cells resistant to cytotoxic drugs. One such cytokine, transforming growth factor-beta (TGF-B1), is a multifunctional peptide that exists in at least five different isoforms in vertebrate species. Recently, there has been a great deal of interest in the role of TGF-B1 as an important multifunctional growth regulator that induces cells of mesenchymal origin to divide while inhibiting the growth of nontransformed epithelial cells. In this study, we combined the effects of the differentiation agent hexamethylene bisacetamide and the inhibiting effects of TGF-B1 on a multidrug-resistant human liver hepatocellular carcinoma and demonstrated the synergistic interaction of these two agents; this synergy resulted in a cell death rate of 80%. These data support the concept of programmed cell death and suggest that drug-resistant tumor cells may be susceptible to the combination of cytokines and differentiating agents.
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PMID:Cytoreductive therapy of multidrug-resistant hepatocellular carcinoma: negative regulation of growth using combination differentiation therapy. 131 33

We have determined the structure of the human ferrochelatase gene after isolation and characterization of lambda phage clones mapping discrete regions of the cDNA. This gene was assigned to human chromosome 18 at region q21.3, by fluorescent in situ hybridization. The gene contains a total of 11 exons and has a minimum size of about 45 kb. The exon/intron boundary sequences conform to consensus acceptor (GTn) and donor (nAG) sequences, and the exons in the gene appear to encode functional protein domains. A major site of the transcription initiation, determined by S1 nuclease mapping, was assigned to an adenine base 89 bases upstream from the adenine base of the translation initiation ATG. The promoter region contains a potential binding site for Sp1, NF-E2 and erythroid-specific transcriptional factor GATA-1, but not a typical TATAA or CCAAT sequence. Analysis of primer extension showed that the transcription starts at the same position between hepatoma HepG2 and erythroleukemia K562 cell mRNA, thereby suggesting that there can be a single transcript in erythroid and non-erythroid cells.
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PMID:Structure of the human ferrochelatase gene. Exon/intron gene organization and location of the gene to chromosome 18. 155 82

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.
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PMID:In vivo footprinting of the human alpha-globin locus upstream regulatory element by guanine and adenine ligation-mediated polymerase chain reaction. 156 44

Murine erythroleukemia (MEL) cells are frequently employed to study both cell growth and erythroid differentiation. Although these cells are easily cultured and induced to differentiate, they are routinely maintained in a medium that contains 10%-15% fetal bovine serum. Because of the variability between different lots and the cost of serum, it was desirable to define a serum-free medium in which to culture MEL cells. In the present work, a totally serum-free, defined medium is described that supports both normal cell growth and dimethyl sulfoxide induced differentiation in the two MEL cell lines examined (DS-19 and 270). A variety of hormones and biological compounds are examined in this medium to determine their effects on growth and differentiation. This medium does not support the growth of the mouse hepatoma cell line.
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PMID:Serum-free, defined medium for the growth and differentiation of murine erythroleukemia cells. 164 93

The influence of fractions of exogenous RNA, isolated from spleens of C3HA mice and of rats, both intact (control--cRNA) and immunized with homogenate of normal syngenic, allogenic and xenogenic tissues (immune--immRNA), on the cytotoxic properties of splenocytes of C3HA intact mice was compared in the in vitro cytotoxic experiments. The splenocytes treated with different RNA fractions were used as effector-cells. In vitro cultivated MGXXIIa cells of strain specific C3HA mice hepatoma, and K562 cells of human erythroleukemia, both labeled with 3H-uridine, served as target cells. Thus, it is only the cytoplasmic fraction of immRNA isolated from the spleens of rats immunized with tissue antigens of C3HA mice that induced a more pronounced stimulation of cytotoxic activity of splenocytes.
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PMID:[Cytotoxic properties of the splenocytes of C3HA mice following treatment with exogenous RNA]. 241 2

To investigate whether a switch in the transcriptional activity of a gene is associated with a change in the timing of replication during the S phase, we examined the replication timing of the beta-globin genes in two different types of somatic cell hybrids. In mouse hepatoma (Hepa 1a) x mouse erythroleukemia (MEL) hybrid cells, the beta-globin gene from the MEL parent is transcriptionally inactivated and is later replicating than in the parental MEL cell line. In human fibroblast (GM3552) x MEL hybrid cells, the human beta-globin gene is transcriptionally activated, and all of the sequences within the human beta-globin domain (200 kilobases) we have examined appear to be earlier replicating than those in the parental fibroblast cell line. The chromatin configuration of the activated human beta-globin domain in the hybrids is relatively more sensitive to nucleases than that in the fibroblasts. Furthermore, major nuclease-hypersensitive sites that were absent in the chromatin flanking the distal 5' region of the human beta-globin gene cluster in the parental fibroblast cell line are present in the transcriptionally activated domain in the hybrid cell line. These results suggest that timing of replication of globin genes has been altered in these hybrid cells and thus is not fixed during the process of differentiation.
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PMID:Activation and repression of a beta-globin gene in cell hybrids is accompanied by a shift in its temporal replication. 279 94

A cell line, CY-1, was selected in tyrosine free (tyr-) medium after fusion of mouse erythroleukemia (MEL) cells with mitomycin C-treated rat hepatoma cells. MEL cells do not express the enzyme phenylalanine hydroxylase (PH) and are unable to grow in tyr- medium, whereas the rat hepatoma cells constitutively express PH and are able to grow in tyr- medium. CY-1 cells resemble MEL cells morphologically, karyotypically, and in being inducible for hemoglobin synthesis. In contrast to MEL cells, CY-1 expresses PH and is therefore able to grow in tyr- medium. Using a rat cDNA probe for the PH gene, Southern blot analyses were carried out on DNA isolated from CY-1 and parental cells. CY-1 showed the characteristic mouse PH gene pattern but the gene copy number was amplified four- to eightfold compared to parental MEL cells.
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PMID:Amplification and expression of phenylalanine hydroxylase in mouse erythroleukemia cells. 298 35


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