Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0345904 (liver cancer)
 15,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Persistent infection with hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC) in humans. HCC has also been observed in animals chronically infected with two other hepadnaviruses: ground squirrel hepatitis virus (GSHV) and woodchuck hepatitis virus (WHV). A distinctive feature of WHV is the early onset of woodchuck tumors, which may be correlated with a direct role of the virus as an insertional mutagen of myc genes: c-myc, N-myc, and predominantly the woodchuck N-myc2 retroposon. In the present study, we searched for integrated GSHV DNA and genetic alterations of myc genes in ground squirrel HCCs. Viral integration into host DNA was detected in only 3/14 squirrel tumors and did not result in insertional activation of myc genes, despite the presence of a squirrel locus homologous to the woodchuck N-myc2 gene. This suggests that GSHV may differ from WHV in its reduced ability to induce mutagenic integration events. However, the high frequency of c-myc amplification (6/14) observed in ground squirrel HCCs indicates that myc genes might be preferential effectors in the tumorigenic processes associated with rodent hepadnaviruses, a feature not reported so far in HBV-induced carcinogenesis. Together with previous observations, our results suggest that hepadnaviruses, despite close genetic and biological properties, may use different pathways in the genesis of liver cancer.
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PMID:Frequent amplification of c-myc in ground squirrel liver tumors associated with past or ongoing infection with a hepadnavirus. 157 Mar 7

The in vitro effect of sodium butyrate (SB) on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T was investigated. SB was added at the non-toxic but cytostatic concentration of 1 mM. In all these cell lines, SB reduced cell proliferation and changed the morphology of the cells into a fibroblast-like shape. In PLC/PRF/5, alpha-fetoprotein production and c-myc expression were inhibited. In contrast, gene expression of albumin, one of the normal liver-cell products, and that of integrated hepatitis B virus genome, was increased. In HCC-M and HCC-T, c-myc expression, which was enhanced in the naive state, was reduced. In HCC-M, fos expression was inhibited but the expression of N- and K-ras genes did not change. SB seemed to induce normal or mature properties of hepatocytes in human hepatoma cell lines.
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PMID:Differentiating effect of sodium butyrate on human hepatoma cell lines PLC/PRF/5, HCC-M and HCC-T. 170 67

A cell line (LCC-18) from a neuroendocrine colonic tumour was established. The tumour cells retained their endocrine characteristics through more than 100 passages and showed positive immunocytochemistry for synaptophysin, vasoactive intestinal polypeptide (VIP) and glucagon. The culture medium also contained VIP and glucagon, which indicates that mechanisms for release of some of the active peptides were preserved. Transplantation of LCC-18 tumour cells into nude rats resulted in tumour formation with similar endocrine characteristics. The c-myc gene was amplified which might have been a prerequisite for establishment of the cell line. The chromosomes in LCC-18 were studied by G-banding and C-banding. The cell line had a distinctive mode in the hypotriploid region, at S = 61. The double minute (Dms) positive stemline karyotype showed numerical and structural aberrations more similar to findings in ordinary colonic adenocarcinomas than to observations in previously studied, pure intestinal neuroendocrine tumours. The Dms may be correlated with amplification of c-myc. LCC-18 may become valuable for studies of neuroendocrine differentiation, regulation of growth and production and release of hormones and for studies of drug effect.
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PMID:Characterisation of a cell line (LCC-18) from a cultured human neuroendocrine-differentiated colonic carcinoma. 178 79

The data reviewed at this meeting reinforce the notion that HBV may contribute to the development of liver cancer through a variety of mechanisms, including activation of oncogenes (c-myc and N-myc) by insertional mutagenesis, expression of viral proteins (X and pre-S2/S) that function as trans-activators and possibly oncoproteins, and introduction of chromosomal defects through enzymatically mediated integration into the host genome. Not all of these mechanisms appear to be active in every tumor, however. Thus, future work will be aimed at characterizing each mechanism in more detail and determining its relative importance in the carcinogenic process.
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PMID:Recent advances in hepatitis B viruses and hepatocellular carcinoma. 198 Aug 25

Dominant-transforming oncogenes are frequently detected in mouse liver tumors, but are rare or inconsistently detected in rat liver tumors. Most of those that have been identified are members of the ras family. While altered expression of many oncogenes has been reported, an increase in the expression of the c-myc gene is consistently observed in both rat and mouse hepatocellular tumors. Both hepatocytes and liver epithelial cells have been immortalized or transformed with viral or cellular oncogenes. Immortalization of cells occurs without the loss of differentiated functions, while transformation induces the expression of many genes/gene products associated with liver cancer in vivo. Cells transformed with chemical carcinogens or oncogenes display a phenotype of growth factor independence or greatly reduced growth factor requirements. Transformation is frequently associated with a substantial decrease in the expression of the exogenous growth factor receptor in the hepatocellular tumors.
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PMID:Oncogene activation and hepatocarcinogenesis. 222 7

Transfection assay of NIH 3T3 cells was performed with DNAs isolated from ten human PHC (primary hepatic cancer) specimens and a hepatoma 7402 cell line. Positive results were obtained in 7402 and in six out of ten PHC DNAs. Human N-ras gene was identified in transfectants from 7402 DNA and transformed cells from three PHC DNA samples, which had passed more than two cycles of transfection. The expression of N-ras was also remarkably enhanced in six out of nine poly(A)+RNA samples isolated from PHC tissues. P21 synthesis was elevated in 7402 cells as well as in transfectants derived from 7402 cells and PHC DNA. In analysis of PHC DNA, rearrangement and amplification of N-ras gene was observed in two PHC samples. The discrepancy of results of the transfection assay and mRNA expression was discussed. Furthermore, c-myc was also highly expressed in most PHC tissues. It implied that the cooperating activity of N-ras and c-myc might be responsible for the malignant phenotypic alteration in some or most cases in human primary liver cancer.
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PMID:Oncogenes in human primary hepatic cancer. 242 30

It is now evident that development of hepatocellular carcinoma (HCC) in human is associated with a long series of cellular and tissue changes that precede the ultimate development of the cancer. During recent years, enormous progress in molecular research on HCC has been made, particularly in the area of integration of HBV DNA to host cell and oncogene association with carcinogenicity. A high ratio of HCCs from patients in endemic area has integrated HBV DNA in cellular DNA and in some cases, chromosomal translocations associated with HBV integration were observed, suggesting that the integration or the results thereof are connected with cancer development. Employing a DNA-mediated transfection assay using NIH3T3 mouse fibroblasts with high molecular weight DNA, we detected three cellular transforming genes (lca, N-ras, hst) in primary human HCC. However, little is known as to the linkage between the activation of these genes and liver carcinogenesis. In most human primary HCC tissues, at least two oncogenes, c-myc and N-ras are overexpressed, while in some cases other oncogenes c-fos or lca are overexpressed. It is likely that multiple c-oncogens are important in HCC, but specific transcripts for the malignancy of HCC were not detected. At present, we could not find any relationship between the expression of c-oncogenes and integration of HBV, serological markers or the degree of differentiation. Of the experimental animals most frequently used for studies of liver cancer, the rat is best understood and mimics closely many of the lesions in humans. It is of interest to consider that the identification and elucidation of the mechanisms underlying carcinogenic processes in the rat may offer testable hypotheses for steps in the human.
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PMID:[Molecular aspects of human hepatocellular carcinoma]. 253 67

Hepatocarcinogenesis is deterministic in transgenic mice expressing in the liver gene construct Alb-DS4 that encodes autocrine growth factor IgEGF (D Stern et al. (1987), Science 235: 321-324), causing their death within 7.1 months. Hepatic expression of construct AAT-myc encoding murine c-myc causes liver cancer in 44% of the mice at 14.8 months. Cooperation of these genes was evident in CD2F1 transgenics bearing Alb-DS4 plus AAT-myc, in which accelerated hepatocellular carcinoma (HCC) formation caused death of all mice within 4.4 months. Alb-DS4 also cooperates with the Hcs locus, which in C3H/HeJ mice mediates high susceptibility to spontaneous hepatocarcinogenesis, causing accelerated formation of HCC to which mice succumbed at 5.1 months. Thus, genes that predispose to HCC formation cooperate in transgenic mice and their interaction is a key to understand mechanisms that cause liver cancer.
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PMID:Autocrine mitogen IgEGF cooperates with c-myc or with the Hcs locus during hepatocarcinogenesis in transgenic mice. 786 54

Liver cell proliferation has often been implicated to play a major role during different steps of the carcinogenic process. Most of the experimental studies indicating a close association between cell proliferation and liver cancer development have made use of a compensatory type of proliferative stimulus. However, liver growth may also be caused by direct hyperplasia after administration of primary mitogens. Our recent studies examined the possible differences between these two types of cell proliferation. Our studies indicate that a) increased expression of proto-oncogenes such as c-fos, c-jun, and c-myc is not necessary for entry into the cell cycle during mitogen-induced liver growth; b) mitogen-induced liver growth does not support initiation of chemical hepatocarcinogenesis; c) repeated proliferative stimuli induced by primary mitogens do not stimulate the growth of initiated cells to a focal and/or nodular stage; and d) mitogen-induced liver growth, unlike compensatory regeneration, is followed by a particular mode of cell death, namely, apoptosis. This type of cell death may be responsible for the elimination of carcinogen-initiated cells.
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PMID:Compensatory regeneration, mitogen-induced liver growth, and multistage chemical carcinogenesis. 801 4

Photobiotin-labelled c-myc gene probe was used to study primary liver carcinoma (PHC) by in situ hybridization on the paraffin sections as well as immunohistochemistry staining for p53 protein expression in 42 cases from high liver cancer incidence regions. The results are as follows: c-myc gene and p53 protein expression were both located in the nuclei. The positive incidences of overexpression of both c-myc gene and p53 protein in PHC were 76% and 55% respectively. The distribution and strength of the overexpression of c-myc gene and p53 protein in PHC are related to the degree of cell differentiation and the overexpression in the liver tissue surrounding the carcinoma is lower than that detected in the PHC tissue.
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PMID:[c-myc gene and p53 protein expression in human primary liver carcinoma]. 808 36


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