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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five simian virus 40 (SV40)-hepatocyte cell lines were examined for tumorigenicity and the effect of in vitro passage on the expression of four liver-specific genes (albumin, transferrin, alpha 1-antitrypsin, and phosphoenolpyruvate carboxykinase), two oncogenes (c-Ha-ras and c-raf), and two genes associated with hepatocarcinogenesis (alpha-fetoprotein and placental-type glutathione-S-transferase). At low passage (12 to 22), all five cell lines expressed the four liver-specific genes at levels similar to those in the liver and were not tumorigenic or were weakly tumorigenic. At high passage (33 to 61), the cell lines formed carcinomas, and four out of five cell lines produced primary tumors that metastasized. At least two cell lines produced well-differentiated hepatocellular carcinomas that expressed liver-specific RNAs. Levels of expression of liver-specific genes changed with time in culture. Some of the changes in liver-specific gene expression in the tumor tissue (such as for the phosphoenolpyruvate carboxykinase gene) paralleled those that occurred with in vitro passage, while other changes (such as for the albumin gene) did not parallel those that occurred with in vitro passage. Correlations between enhanced expression of c-Ha-ras and tumorigenic potential and between the process of SV40 immortalization and induced expression of c-raf and glutathione-S-transferase-P were observed. Induction of alpha-fetoprotein was detected with in vitro and in vivo passage only in the CWSV14 cell line and was paralleled by diminished albumin expression. In conclusion, we developed a model system with five SV40-hepatocyte cell lines, tumors induced by them, and tumor cell lines to examine changes in gene expression that accompany the progression from a normal cell to a hepatocellular carcinoma. Because the SV40-hepatocyte cell lines and tumor cell lines remain highly differentiated and vary in the magnitude of expression of specific genes, they can be used to study the molecular mechanisms regulating gene expression, in particular those regulating specific genes associated with differentiation.
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PMID:Tumorigenicity of simian virus 40-hepatocyte cell lines: effect of in vitro and in vivo passage on expression of liver-specific genes and oncogenes. 246 Jul 44

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

Tumorigenicity and oncogene expression were examined in HepG2 derived cells, a human hepatoma cell line. HepG2 cells and a single cell clonal HepG2 line, HLD2-6, were equally tumorigenic when injected s.c. into athymic nude mice. Cyclophosphamide pretreatment of both cell lines (500 micrograms cyclophosphamide/ml/two cell cycles) had no effect on tumor incidence or latency (P greater than 0.05). Tumors were nonencapsulated, highly invasive adenocarcinomas and were positive for gamma-glutamyltranspeptidase activity and bile production. Plasma from tumor-bearing mice was positive for human alpha-fetoprotein and negative for hepatitis B virus surface antigen as measured by radioimmunoassay. Two cell lines reestablished into tissue culture from HLD2-6 derived tumors had unaltered cell cycle times. Detailed in vitro translation analysis of RNA isolated from HLD2-6 derived cells and tumors were extremely similar to the translation products of RNA isolated from a normal human liver sample except for a Mr 53,000 polypeptide with an apparent charge shift. c-myc specific transcripts, when compared to a normal human liver sample, were increased in all HLD2-6 cell lines and tumors derived from HLD2-6 cells. This increase in c-myc expression could not be explained by gene amplification or hepatitis B virus integration. N-ras specific transcripts were not elevated in HLD2-6 cells grown in tissue culture but there was a selective increase of the 5.5-kilobase N-ras transcript in HLD2-6 derived tumors grown in nude mice. This increased 5.5-kilobase transcript did not remain elevated if the tumors were reestablished into tissue culture, suggesting some interaction with the host animal. c-Ha-ras expression could not be detected in any HLD2-6 derived tumor or cell line.
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PMID:Tumorigenicity and transcriptional modulation of c-myc and N-ras oncogenes in a human hepatoma cell line. 299 77

The expression of 7 cellular oncogenes in a human hepatoma cell line PLC/PRF/5 was studied using Northern blot analyses. Among the oncogenes tested, c-abl, c-fes, c-fms, c-myc, c-Ha-ras and c-sis were expressed. The oncogene c-Ki-ras was not expressed. The length of the mRNAs expressed was almost consistent with published data. Compared to the oncogene expression in Daudi lymphoma cells, the same kind of oncogenes were expressed in PLC/PRF/5 cells, but the intensity of the signal in each oncogene expression was stronger in Daudi cells than in PLC/PRF/5 cells. Considering the cellular localization and the function of each oncogene, the oncogene survey in hepatoma cells broadens the knowledge of hepatocarcinogenesis and the character of human hepatoma cells.
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PMID:Oncogene expression in human hepatoma cells PLC/PRF/5. 300 83

Expression and activation of several c-oncogenes in seven hepatocellular carcinomas from seven separate rats treated with aflatoxin B1 (AFB1) were examined by Northern and Southern blot analyses. Both c-Ha-ras and c-myc transcripts were elevated at high levels in all hepatomas. Moreover, in one of them, T2-1 hepatoma, the c-myc gene was amplified only in a tumor part of liver without significant rearrangement. N-ras specific transcripts were not elevated in these hepatomas. The present data suggest that the consistently increased expression or deregulation of the c-myc and c-Ha-ras genes may play an important role in the development of hepatomas induced by AFB1.
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PMID:Expression of the c-Ha-ras and c-myc genes in aflatoxin B1-induced hepatocellular carcinomas. 301 42

DNA was extracted from NIH 3T3 cells transformed with DNAs from human primary hepatic cancer (PHC) and Hepatoma 7402 cell line. The transformant DNA was analyzed by Southern transfer and hybridization with 32P-labeled probes of various oncogenes. The EcoRI 7.2 and 9.0 kb bands characteristic of human N-ras gene were identified in transformed NIH 3T3 cells derived both from PHC and 7402 DNA. The BamHI 6.6 kb band characteristic of human c-Ha-ras I was present only in 7402 transformants, but not in PHC transformants. Using 35S-methionine incorporation, immunoprecipitation with anti-p21 monoclonal antibodies, SDS-PAGE and autoradiography, it was demonstrated that p21 synthesis was remarkably enhanced in 7402 cells as well as in transformed cells derived from both 7402 and PHC DNA. Taking the data together, it strongly implies that N-ras is one of the transforming genes for human liver cancer.
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PMID:Identification of human N-ras as the common oncogene in NIH 3T3 cells transformed with DNAs from human primary hepatic cancer and hepatoma 7402 line. 301 22

When Chinese hamster lung (CHL) cells were cultured in medium containing 25 microM cadmium chloride, resistant cells appeared at a frequency of 0.04%. When one of three tumor promoters, 12-O-tetradecanoylphorbol-13-acetate (TPA), aplysiatoxin and dihydroteleocidin B, was added during selection with cadmium chloride, the frequency of appearance of resistant cells increased more than 50-fold. Two of the resistant clones obtained were characterized. Both clones produced much higher levels of metallothionein I mRNA than the parental CHL cells. Southern blot analysis showed that in these resistant cells, metallothionein I genes were amplified approximately 5-fold. Therefore, it seems that tumor promoters can enhance the frequency of gene amplification. One possible mechanism of the action of tumor promoters in oncogenesis is amplification of activated c-onc genes. Consistent with this idea, it has been reported that c-onc genes are amplified in various cancer cells. We also found that the c-Ha-ras and c-myc genes were amplified in a bladder cancer removed surgically and in a transplanted rat hepatocellular carcinoma, Morris hepatoma 7794A, respectively.
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PMID:Increase in frequency of appearance of cadmium-resistant cells induced by various tumor promoters; evidence for the induction of gene amplification. 668 Jul 25

Expressions of the c-Ha-ras and c-myc genes were studied by Northern blotting of total RNA from primary tumors and non-tumorous parts of the liver of rats given diet containing 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and from established rat hepatoma cell lines. The expression of the c-Ha-ras gene was found to be high in the primary tumors, non-tumorous parts of 3'-Me-DAB-treated livers and hepatoma cell lines. In contrast, the c-myc gene was expressed at a high level only in primary tumors and hepatoma cell lines. During 3'-Me-DAB treatment, the c-Ha-ras mRNA level in the liver increased by day 5 and then remained high. Increase in expression of the c-Ha-ras gene in regenerating liver was confirmed. These findings suggest that increase in expression of the c-Ha-ras gene is related to proliferation of hepatocytes, whereas expression of the c-myc gene is associated with hepatocarcinogenesis.
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PMID:Expressions of the c-Ha-ras and c-myc genes in rat liver tumors. 671 68

Expression of oncogene mRNA was investigated in 37 cases of hepatocellular carcinoma (HCC) surgically resected using in situ hybridization (ISH) technique. C-myc, c-Ha-ras and N-ras DNA probes labeled with biotin were used. The hybrids were detected by streptavidin-biotin alkaline phosphatase staining. Thirteen cases of liver cirrhosis and 16 cases of non-cirrhotic liver were also examined as controls. In HCC cases, c-myc mRNA was expressed in 15 of 37 cases. The c-myc positive cells were found unevenly both in cancerous regions and in non-cancerous regions, being mainly distributed near the cancer capsule. The hybrids were detected mostly in cytoplasm of cancer cells. In some cases, they were seen not only in the parenchymal cells but also in the non-parenchymal cells, such as histiocytes, Kupffer cells and fibroblastic cells. In control cases, c-myc mRNA was expressed in five of 13 cases of liver cirrhosis and in three of 16 cases of non-cirrhotic liver. The expression of c-Ha-ras mRNA could be detected in only three of 37 cases of HCC. These three cases were early staged HCC. The expression of N-ras mRNA was detected in five of 32 cases examined of HCC. These five cases were differentiated type HCC. These results suggest that c-myc gene might play an important role in evolution and progression of HCC, and that ras genes might play a role in hepatocarcinogenesis at early stage.
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PMID:[Study on the expression of oncogene mRNA in hepatocellular carcinoma using in situ hybridization technique]. 783 Jul 8

It has been observed that certain rare alleles of the c-Ha-ras gene occur more frequently in patients with certain malignant tumors than in healthy individuals, suggesting that these alleles may serve as markers for particular types of cancer. In this study, we compared the restriction fragment length polymorphism at the c-Ha-ras gene locus in 40 patients with cirrhosis and hepatocellular carcinoma with that in 39 patients with cirrhosis and in 42 normal subjects, all of Caucasian origin. Southern blotting of leukocyte DNA from the above patients, after digestion with either BamH1 or AvaII, revealed the presence of allele fragments of different sizes, corresponding to 4 common alleles and 3 rare alleles. The occurrence of the 3 rare alleles was not significantly different in the 3 populations studied. On the other hand, 2 of the common alleles, a3 (P < 0.01) and a4 (P < 0.03), were found at a significantly higher frequency in patients with cancer than in the 2 other groups. These results suggest that, in hepatocellular carcinoma, there is no increase in the frequency of occurrence of the rare alleles of the c-Ha-ras, but that the distribution of the common alleles may be modified.
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PMID:c-Ha-ras polymorphism in patients with hepatocellular carcinoma. Comparison of healthy subjects and alcoholic patients with cirrhosis. 790 2


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