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 have investigated the regulation of metallothionein gene expression in two fish cell lines. Rainbow trout hepatoma (RTH) cells synthesized metallothionein in response to heavy metal exposure. The maximum level of metallothionein synthesis detected during zinc exposure was much greater than during cadmium exposure. The time-courses of metallothionein synthesis were different for the different metal inducers, suggesting that metallothionein may be differentially regulated by cadmium and zinc in these cells. The metal-induced synthesis of metallothionein was correlated with increased translational activity and accumulation of metallothionein-mRNA, suggesting that metallothionein may be regulated at the transcriptional and post-transcriptional levels in RTH cells. Chinook salmon embryo (CHSE) cells, unlike RTH cells, did not synthesize metallothionein or metallothionein-mRNA in response to heavy metal exposure. However, when these cells were treated with 5-azacytidine prior to heavy metal exposure, the synthesis of metallothionein was induced, suggesting that DNA methylation may play a role in metallothionein gene expression in fish.
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PMID:Metallothionein gene expression in fish cell lines: its activation in embryonic cells by 5-azacytidine. 243 33

The human metallothioneins are represented by a multigene family consisting of about 14 members. A number of MT-like genes have been isolated from a human genomic library and in this report, four MT genes have been characterized. Our results show that two of these genes represent the MT-I and MT-II processed genes. The other two genes (MT-IF and MT-IG) are functional members of the MT-I gene family. The amino acid sequence encoded by the MT-IF and MT-IG genes differ from the amino acid sequences of the published MT-I proteins at few positions. The 5'-flanking region of these genes contain metal responsive elements. Our studies show that the MT-IF and MT-IG genes are differentially regulated in two human hepatoma cell lines, HepG2 and Hep3B2, and a human lymphoblastoid cell line, WI-L2 in response to the heavy metals cadmium, zinc and copper, and glucocorticoids. In addition, these genes also show cell-type specific expression.
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PMID:Structure and expression of the human metallothionein genes. 244 57

The rainbow trout hepatoma (RTH) cell line responds to heavy metals such as zinc and cadmium by synthesizing the ubiquitous thiol-rich protein metallothionein (MT). From this cell line we have isolated two full-length cDNA clones, tMT-A and tMT-B, which encode two similar but distinct trout MTs. The clones were isolated by cross-homologies between the trout MT mRNAs and a human MT riboprobe. Clones tMT-A and tMT-B code for proteins of 61 and 60 amino acids, respectively; the one extra amino acid in tMT-A is due to an apparent insertion at position 31 of the protein. There are also two other amino acid changes between the two isoforms. Overall, the coding regions show extensive homologies to mammalian MTs, especially at the cysteine residues and at a core sequence at the boundary of the two domains. However, closer examination reveals a number of significant differences in positions usually invariant in the mammalian MTs. Northern blot analysis of RNA from metal-treated RTH cells demonstrated MT-mRNA is induced to high levels by zinc, low levels by cadmium, and minimally by copper. In contrast, intraperitoneal injections of rainbow trout demonstrated that all three metals induce MT-mRNA to comparable levels in the liver. Southern blot analysis of trout DNA cleaved with three restriction enzymes suggests that the trout family of MT genes is probably limited to these two members.
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PMID:The rainbow trout metallothioneins: molecular cloning and characterization of two distinct cDNA sequences. 244 99

We have examined the effect of heavy metals on the expression of two major groups of stress-induced proteins in fish cell lines: the 70 kDa heat-shock proteins (hsp70) and metallothioneins (MTs). The rainbow trout hepatoma (RTH) cell line synthesized the hsp70 protein in response to zinc and heat shock, while chinook salmon embryonic (CHSE) cells synthesized this protein in response to these inducers, as well as cadmium. The synthesis of this 70 kDa protein was correlated with the accumulation of hsp70 mRNA as measured by hybridization to a trout hsp70 gene probe. Heavy metals also induced the synthesis of MT in RTH cells. However, heat shock did not result in induction of MT and its mRNA. Unlike RTH cells, CHSE cells did not synthesize MT following exposure to cadmium or zinc. When these cells were treated with 5-azacytidine prior to heavy metal treatment, accumulation of MT mRNA was observed. Northern blot analysis of total RNA from 5-azacytidine treated CHSE cells, using a trout MT (tMT-B) cDNA probe, indicated that the time-course of induction and the maximal level of MT mRNA accumulation in response to cadmium and zinc paralleled that observed in RTH cells. Copper and dexamethasone were ineffective in inducing MT mRNA in 5-azacytidine-treated CHSE cells. These results indicate that MT is specifically induced in response to heavy metal treatment, whereas the synthesis of hsp70 appears to be a general stress response. Furthermore, MT is differentially regulated by heavy metals and dexamethasone in these cell lines and the expression of MT is cell-type-specific.
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PMID:Analysis of stress-induced gene expression in fish cell lines exposed to heavy meals and heat shock. 246 89

Intracellular zinc was located as electron dense granules associated with the plasma membrane, endoplasmic reticular membranes, mitochondrial membranes, nuclear membranes and chromatin in Zajdela ascitic hepatoma and AK5 macrophage ascitic tumour cells. The quantity of intracellular zinc estimated by atomic emission spectrometer was different in the two cell lines. However, after loss of permeability control by the plasma membrane, involving glutaraldehyde and heat-shock treatments, the quantity of intracellular zinc was increased to almost the same extent in both cases.
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PMID:Localization of intracellular zinc under conditions of altered permeability control of the plasma membrane. 251 51

It has been pointed out that hepatocellular carcinoma (HCC) develops more frequently in cirrhotic liver with siderosis than in liver without iron deposition, that excess copper in hepatocytes inhibits hepatocarcinogenesis, and that an increase in copper and a decrease in zinc are seen in the sera of patients with various malignant tumors. Iron, copper and zinc concentrations in the serum and liver were estimated in normal subjects and cirrhotic patients with and without HCC. Serum copper level was significantly higher in cirrhotic patients with or without HCC than in normal subjects. No significant differences were observed in the levels of these trace elements in the serum and liver of cirrhotic patients with and without HCC. The current study seems to indicate that iron, copper and zinc do not play an important role in the development of HCC in cirrhotic patients in Japan.
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PMID:Iron, copper and zinc levels in serum and cirrhotic liver of patients with and without hepatocellular carcinoma. 255 Aug 61

In separate studies, radioisotopes 65Zn and 86Rb were used to monitor trace element fluctuations from normal in C57L/J mice throughout the progression of a murine hepatoma. Amounts too small to upset normal levels were injected directly into the blood stream. After an equilibration period, the whole mouse and various resected organs and tissues were counted. Compared to normal levels, rubidium in diseased mice was lower in kidney and blood, and elevated in skin and muscle. Diseased mice showed depressed levels of zinc in skin and muscle. Large fluctuations during different stages of tumor growth were observed for various other tissues and organs of diseased mice.
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PMID:Rubidium and zinc fluctuations in selected tissues during the development of the BW7756 murine hepatoma. 261 24

Since zinc is essential for the proliferation of tumor cells, the growth of tumor cells is suppressed in the zinc deficient condition. Thus, administration of progesterone, which decreases zinc uptake of tumor cells, to tumor bearing rats may inhibit the tumor growth. From this aspect, the antitumor effect of progesterone alone, or in combination with various anticancer drugs was investigated in the rats bearing Yoshida sarcoma (YS) or ascites hepatoma 109A (AH 109 A). In YS bearing rats, a significant inhibition of the tumor growth in size was observed by progesterone, and a slight inhibition of the tumor growth in AH 109 A bearing rats. A decreased zinc content of YS cells was also observed in YS bearing rats given progesterone in comparison with that of control rats. In combination of progesterone and anticancer drugs, the antitumor effect of methotrexate or vincristine was markedly enhanced by progesterone in YS bearing rats.
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PMID:[Experimental studies on the antitumor effect of progesterone and enhancement of the therapeutic effect of anticancer drugs by progesterone--from the aspect of zinc metabolism]. 275 19

1. The possibility of an effect of zinc on the rate of tumour cell division, mediated through a regulation of cellular cAMP concentration, was investigated in the present study in rats. 2. Dietary Zn deficiency (less than 1.5 mg Zn/kg) but not Zn excess (500 mg Zn/kg) resulted in an increased cAMP concentration in transplanted hepatoma cells. Neither treatment had any effect on the cAMP concentration in regenerating liver or normal resting liver. Both the deficient and excess Zn diets resulted in a small reduction in tumour growth (not statistically significant). 3. The results seem to indicate that the relation investigated in the present study does not apply in the cell line used.
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PMID:A possible relation between dietary zinc and cAMP in the regulation of tumour cell proliferation in the rat. 284 Jan 15

The regulation of heavy metal induced gene expression was investigated in two fish cell lines: the rainbow trout hepatoma (RTH) and Chinook salmon embryo (CHSE) cells. The induction of metallothionein (MT) synthesis occurred in RTH cells exposed to zinc, and to a lesser extent, following exposure to cadmium. The time courses of MT synthesis were different for the different metal inducers, suggesting that MT may be differentially regulated in these cells. CHSE cells, unlike RTH cells, did not synthesize MT in response to metal treatment. Treatment of the cells with 5-azacytidine prior to heavy metal exposure resulted in the induction of MT synthesis. Since these cells were embryonic in origin, these findings raised the possibility that MT gene expression may be developmentally regulated in fish. Analysis of the entire spectrum of cellular proteins has revealed the synthesis of an unknown, 14,000 dalton, metal-inducible protein (MIP) and various stress proteins following exposure of fish cells to heavy metals.
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PMID:Heavy metal induced protein synthesis in fish cell lines. 295 36


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