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 ras gene is one of the oncogenes most commonly detected in human cancers, and it consists of three families (H-ras, K-ras, N-ras). These genes are converted to active oncogenes by point mutations occurring in either codon 12, 13, or 61. We analyzed mutations of these codons in 23 primary hepatic malignant tumors (12 hepatocellular carcinomas, nine cholangiocarcinomas, and two hepatoblastomas) by a method to directly sequence nucleotides, using polymerase chain reaction and a direct sequencing method. Of 23 hepatic malignant tumors, point mutations at K-ras codon 12 or K-ras codon 61 were found in six of nine cholangiocarcinomas. In contrast, there were no point mutations in any of 12 hepatocellular carcinomas or two hepatoblastomas around codon 12, 13, or 61 of the ras genes. These observations suggest that ras gene mutations are not related to pathogenesis of hepatocellular carcinoma, but play an important role in pathogenesis of cholangiocarcinoma.
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PMID:Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing. 215 51

The expression of the c-myc gene has previously been shown to be elevated and deregulated in the human hepatoma cell line Hep G2 (B. E. Huber and S. S. Thorgeirsson, Cancer Res., 47: 3414-3420, 1987). We now report that the Hep G2 N-ras gene is activated to a dominant-acting, transforming gene by a missense mutation in codon 61. Hep G2 DNA produced transformed foci when transfected into NIH 3T3 cells. Subsequent to a secondary round of transfection, Southern blot analysis of tumorigenic NIH 3T3 foci demonstrated the presence of human N-ras sequences. Nucleotide sequence analysis of one Hep G2 N-ras allele demonstrated that codons 12, 13, and 59 were normal and that codon 61 had a missense mutation (CAA to CTA). This mutation results in the incorporation of leucine instead of glutamine at residue 61 of the N-ras gene product, p21. N-ras sequences were amplified by the polymerase chain reaction from both Hep G2 genomic DNA and Hep G2 complementary DNA. Analysis of the amplified sequences demonstrated that only one Hep G2 N-ras allele exhibited the codon 61 mutation and that both the mutant and normal alleles were transcribed. Northern blot analysis demonstrated equivalent steady-state levels of N-ras transcripts in Hep G2 cells and normal human liver. The steady-state levels of N-ras and ornithine decarboxylase transcripts were positively correlated suggesting a positive relationship between N-ras expression and the replication rate of Hep G2 cells. c-Ki-ras and c-Ha-ras transcripts were not detected in either Hep G2 cells or normal human liver. Immunoprecipitation experiments using the monoclonal antibody Y13-259 demonstrated the presence of p21 in Hep G2 cells. Expression of a dominant-acting, transforming N-ras gene, in conjunction with the altered regulation of the c-myc gene, documents two important genetic lesions that could be responsible for the transformed phenotype of Hep G2 cells.
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PMID:Characterization of a transforming N-ras gene in the human hepatoma cell line Hep G2: additional evidence for the importance of c-myc and ras cooperation in hepatocarcinogenesis. 215 25

To study the possible role of proto-oncogenes in the multistep process of human liver hepatocarcinogenesis, we have examined the expression of c-N-ras and c-myc in human hepatocellular carcinomas and liver tissue surrounding the tumors as well as cirrhotic livers which are generally considered to precede the formation of human hepatocellular carcinoma. One to four-fold higher expression of the c-N-ras proto-oncogene was observed in twelve hepatoma patients as compared to normal liver. Increased expression of c-N-ras was also observed in liver tissue surrounding these tumors. Eight patients exhibited an apparent higher expression of the c-N-ras oncogene in adjacent liver tissue than in their corresponding tumor tissues. Six human liver cirrhosis patients also exhibited a slight increase in c-N-ras expression. Southern blot analysis demonstrated an amplified c-N-ras sequence in these tissues surrounding the tumors. In the study of the c-myc gene, variable degrees of highly enhanced expression were found in all twelve hepatoma patients as compared to normal liver. The c-myc gene was also expressed in the adjacent liver tissue and in some of the human cirrhotic livers. Our studies give further evidence that the expression of c-N-ras and c-myc proto-oncogenes are involved in the process of human hepatocarcinogenesis.
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PMID:The expression of c-myc and c-N-ras in human cirrhotic livers, hepatocellular carcinomas and liver tissue surrounding the tumors. 216 54

With DNA-mRNA hybridization in situ technique, the expression of five oncogenes, c-N-ras, c-K-ras, c-H-ras, c-myc and c-fos, was observed in two cases of human hepatocellular carcinoma. The expression of c-N-ras, c-fos was greatly enhanced in tumor tissues of the two cases, and about 25%-50% of the tumor cells showed positive expression. The other three oncogenes namely c-K-ras, c-H-ras and c-myc, were not detected in these two carcinomas or the non-cancerous liver tissue adjacent to the carcinomas. It is surmised that c-N-ras and c-fos may play coordinative role in maintaining the malignant phenotype of human primary hepatocellular carcinoma.
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PMID:[Expression of cellular oncogenes in human primary liver cell carcinoma]. 216 75

The effects of lycobetaine (LBT) on DNA single strand break and chromatin conformation were examined by in-situ nick translation method. It was found that LBT did not cause DNA single strand break. After 2-h incubation of murine hepatoma cells with 1-50 micrograms/ml LBT in vitro, the chromatin transcription activity was inhibited gradually. This effect was time- and dose-dependent. Actinomycin D produced a similar effect; 10-hydroxycamptothecin not only caused DNA single strand break, but also altered chromatin conformation; homoharringtonine had no marked influence on either. By molecular hybridization technique, it was found that the effect of LBT on individual genes was somewhat different. After 2-h incubation of the cells with LBT, the sensitivities of c-myc, N-ras, and beta 2-microglobulin genes to DNase I were decreased from 75 +/- 6, 66 +/- 4, 70 +/- 8% to 28 +/- 8, 25 +/- 5, 28 +/- 7%, respectively, while that of c-myb and beta-globin genes (8 + 6%, 6 + 5%) did not change obviously.
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PMID:Effects of lycobetaine on chromatin structure and activity of murine hepatoma cells. 228 45

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

In order to characterize the genes overexpressed in an hepatoma cell line, the HTC cells, and in diethylnitrosamine induced solid hepatomas, we constructed a complementary DNA library from HTC cells and performed differential screening with probes from HTC cells, from malignant nodules obtained 70 weeks after the carcinogen treatment, and from hepatocytes from normal rat liver. Eight clones corresponding to messenger RNAs (mRNAs) much more expressed in hepatomas than in hepatocytes from normal liver were isolated. Three, clones pHT 71, pHT 13, and pHT 26, were further analyzed by the study of their corresponding transcripts in hepatocytes from regenerating liver and in the hepatocytes from the nontumorous parts of the liver. Clone pHT 71 corresponds to a single 2.3-kilobase mRNA which is present in high levels in carcinoma nodules in hepatoma cell lines, in the nontumorous parts of the liver, and in hepatocytes isolated from regenerating liver 30 h after partial hepatectomy. Clone pHT 13 hybridizes with three distinct transcripts 3.8, 2.6, and 1.6 kilobases long. High levels of the 3.8- and 1.6-kilobase mRNAs are present in carcinoma nodules, in hepatoma cell lines, and in the nontumorous parts of the liver. However, the levels of these RNAs are similar in hepatocytes from regenerating liver and in hepatocytes obtained from normal rat liver. Clone pHT 26 corresponds to a 0.6-kilobase mRNA which exists at a high level only in cancer nodules and in hepatoma cell lines. We were unable to observe any cross-hybridization between these clones and the oncogenes which have been found to be expressed in hepatomas (c-fos, c-Ha-ras, c-Ki-ras, N-ras, and c-myc). The mRNAs corresponding to the three clones have not been detected in various tissues from normal adult rats. Our study shows that a high level of these mRNAs might be associated with rat liver carcinogenesis.
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PMID:Isolation and characterization of complementary DNA clones for genes overexpressed in chemically induced rat hepatomas. 242 72

The development of chemically induced hepatocellular carcinoma in the rat proceeds through a series of premalignant changes that may ultimately progress to a primary malignant tumor. Using the selection technique based on diminished binding of preneoplastic hepatocytes to tissue culture plates precoated with asialofetuin, we have isolated poly(A+)RNA from early preneoplastic foci as well as preneoplastic persistent nodules and primary hepatocellular carcinoma induced by the Solt-Farber protocol in the Fischer rat. The steady-state poly(A+)RNA levels of genes traditionally associated with growth, differentiation and/or transformation were then determined to address the question of their temporal expression in the multistep nature of cancer development. Ornithine decarboxylase- and P53-specific transcripts did not significantly change in preneoplastic foci but were increased in later-stage preneoplastic nodules and hepatocellular carcinoma. Albumin-specific transcripts were decreased in all hepatocellular carcinoma but there was no consistent coordinated increase in alpha-fetoprotein-specific transcripts. c-myc and raf transcripts increased at the very early preneoplastic foci stage and continued to increase throughout the neoplastic process. No L-myc or N-myc transcripts could be detected in any RNA sample. c-Ha-ras-specific transcripts were essentially unaltered in all RNA samples whereas no c-Ki-ras or N-ras transcripts could be detected throughout the neoplastic process. In addition, no dominant-acting transforming mutations in the ras gene family were detected by DNA transfection experiments using NIH/3T3 cells.
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PMID:Poly(A+)RNA levels of growth-, differentiation- and transformation-associated genes in the progressive development of hepatocellular carcinoma in the rat. 246 94

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

Activated N-ras gene was isolated from human hepatoma tissue by DNA transfection assay coupled with the neomycin selection method and molecular cloning and a point mutation in the codon 61 (CAA----AAA) was noted. However, examination of the proportion of the mutated N-ras gene in the tumor part by molecular cloning and by hybridization using synthetic oligonucleotide probes indicated that the mutated gene occurred with very low frequency. The activated N-ras gene appears located only in a small fraction of the tumor cells. The experimental data indicate activation of this gene as possibly not the major cause of carcinoma, but rather a manifestation of tumor heterogeneity.
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PMID:Activated N-ras gene was found in human hepatoma tissue but only in a small fraction of the tumor cells. 253 92


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