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)

A recombinant retroviral vector was constructed which expressed antisense RNA of c-ets-2, c-myc and N-ras. The pseudotype virus was packaged and rescued by transfection in PA317 cells and used to infect human hepatoma cell line SMMC-7721. After selection with G418, resistant colonies were obtained. Stable integration of retrovirus in infectants was shown by Southern hybridization of genomic DNA and the presence of antisense RNA was detected by RNA dot blot hybridization. It was demonstrated that the antisense RNAs did inhibit the growth of human SMMC-7721 hepatoma cells. The ability to form colony in soft agar and tumorigenicity in nude mice of SMMC-7721 were significantly suppressed by the antisense RNAs. The result implicates the potential value in future cancer gene therapy.
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PMID:[Reversal of malignant phenotype of human hepatoma cells by antisense c-ets-2, c-myc and N-ras]. 780 49

We have established two cell lines of hepatocellular carcinoma [Hep-KANO, clone 1 (CL-1) and clone 2 (CL-2)] from tissue obtained at autopsy of a hepatitis B virus (HBV) carrier without histological signs of hepatitis or liver cirrhosis. These cell lines differed considerably from each other in morphology, proliferation pattern, alpha-fetoprotein secretion, albumin synthesis, cytokine secretion, modal chromosome number and transplantability to nude mice. Histologic examinations also revealed differences between them. Amplification of N-myc, L-myc, H-ras, K-ras, N-ras, c-erb-B and c-erb-B-2 and rearrangement of p53 were not found in either of the cell lines. However, CL-1 and CL-2 showed an identical HBV-DNA integration pattern. A 4-fold amplification of c-myc was observed in CL-1, but not in CL-2. Hep-KANO cell lines, CL-1 and CL-2 may be useful in clarifying the question of whether hepatocarcinogenesis is directly caused by HBV infection.
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PMID:Characteristics of human hepatocellular carcinoma cell lines (Hep-KANO) derived from a non-hepatitic, non-cirrhotic hepatitis B virus carrier. 782 95

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

Altered expression of protooncogenes/oncogenes is believed to be involved in hepatocarcinogenesis of the chemically induced, transplantable Morris hepatoma 7777. We compared the mRNA expression of c-N-ras and v-erb B mRNA of normal rat liver with that of Morris hepatoma 7777 using Northern blot analysis and in situ hybridization. Northern blot analysis revealed a strong overexpression of the v-erb B related mRNA, while the c-N-ras mRNA was only slightly increased. In situ hybridization using a c-N-ras mRNA probe also showed only a slightly increased number of silver grains in the hepatoma cells compared with normal rat liver. On the other hand, the v-erb B related mRNA was strongly overexpressed in the hepatoma cells, while the connective-tissue capsule, the blood vessels, blood cells and the necrotic foci did not show an elevated v-erb B related gene mRNA expression. Similar results were obtained in liver metastases. The detectable v-erb B hybridization signal was lost by pretreatment with RNase A. We conclude that the c-N-ras gene is of minor importance in the chemically induced, transplantable Morris hepatoma 7777, while the increased expression of the v-erb B related mRNA is due to a selection of ligand-independent tyrosine kinase activity.
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PMID:Expression of the erb B oncogene in the Morris hepatoma 7777. 786 26

A series of changes in the genes that control hepatocyte growth, or interference with the protein products of these genes, appears to have an important role in the etiology of hepatocellular carcinoma (HCC). Mutations of the p53 tumor suppressor gene have been identified in 30-50% of HCC patients in some geographic areas. Abnormalities of the RB tumor suppressor gene have been found in 20-25% of HCCs, including 80-86% of HCCs with p53 mutations. Overexpression of transforming growth factor alpha (TGF-alpha), insulin-like growth factor II (IGF-II), and the oncogenes N-ras, c-myc, and c-fos have been found in high percentages of HCC patients. The cumulative effect of these changes may be more important than the order in which they occur. Some of these changes may explain the mechanism(s) by which the hepatitis B virus participates in the development of HCC.
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PMID:Tumor suppressor genes, growth factor genes, and oncogenes in hepatitis B virus-associated hepatocellular carcinoma. 804 25

A G:C-->T:A mutational hotspot at codon 249 of the p53 tumor suppressor gene has previously been identified in hepatocellular carcinoma (HCC) of patients from Qidong, China and southern Africa in which aflatoxin B1 (AFB1) and hepatitis B virus (HBV) are known synergistic risk factors. We have examined p53 mutation patterns of HCC from geographic areas in which the risk factors vary. Nine HCC lines and four hepatoblastoma lines (HB) were examined for p53 gene mutations and the relationship with HBV infection. Five of the nine HCC lines had homozygous mutation or deletion randomly distributed in exons 6-8, whereas none of the four HB cell lines had p53 mutations. One of the four HB lines (HepG2) had an N-ras mutation at codon 61 position 2. The p53 point mutations in the three HCC cell lines from Japan resulted in the amino acid changes of cysteine for tyrosine in cell line HuH 7 at codon 220 (A:T-->G:C), alanine for glycine in cell line HLF at codon 244 (G:C-->C:G), and serine for arginine in cell line HLE at codon 249 (G:C-->C:G). In addition, the deletion of 18 base pairs from codon 264 position 3 to codon 270 position 1 has resulted in the deletion of Leu-Gly-Arg-Asn-Ser-Phe from the amino acids sequences 256-270 in the Japanese cell line HuH 4. The cell line PLC/PRF/5 that showed p53 mutation at codon 249 (G:C-->T:A) with substitution of serine for arginine was derived from a South African patient. Our results indicate that whereas the p53 gene is not mutated in the HB cell lines, the HCC cell lines frequently contain an abnormal p53 gene. In addition, p53 point mutations were not detected in the four Japanese HCC cell lines that were positive for genomic integration of HBV X-gene and surface antigen gene. The three Japanese HCC cell lines with p53 mutations did not contain HBV sequences, indicating that hepatocarcinogenesis associated with p53 mutation does not require the genomic integration of HBV sequences.
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PMID:p53 gene mutation and integrated hepatitis B viral DNA sequences in human liver cancer cell lines. 838 56

In order to investigate the action of oncogenes in experimental hepatocarcinogenesis, the expression of c-myc, N-ras and H-ras were studied during early and late stages of DENA induced hepatocarcinogenesis in rats by using in situ hybridization. The results showed that overexpression of c-myc and N-ras was presented in teh proliferation hepatocytes and alternated hepatocytes foci during the early stage of hepatocarcinogenase, and with the formation and progression of hyperplastic hepatocytic nodules, the overexpresion cells of both were increased and often accompanied each other. Overexpression of H-ras appeared in the middle stage of hepatocarcinogenesis. The data obtained indicate that the abnormal expression of N-ras and c-myc in the hepatocarcinogenesis is not only an earlier molecule event which may relate to the initiation of HCC, but also the molecular basis for the morphogenesis of HCC, and these two functions took synergically. However, the abnormal expression of H-ras may have a promotive effect on the development of preneoplastic lesions, and also suggests that the malignant transformation of hepatocyte needs the cooperation of multiple oncogenes.
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PMID:[In situ expression of c-myc, N-ras during diethylnitrosamine induced hepatocarcinogenesis]. 874 81

The expression of PCNA and the protooncogenes of ras family (N-ras, H-ras and Ki-ras) in hepatocarcinoma cells and the proliferating liver cells in precancerous, hyperplastic nodules during experimental hepatocarcinogenesis, induced by diethylnitrosamine in rat liver was observed immunohistochemically and by in situ hybridization. The results indicated that there was a positive expression of PCNA in both the carcinomas cells and precancerous liver cells. The amount of PCNA-positive cells exhibited a negative correlation with the amount of infiltrating mast cells surrounding carcinoma cell nests and the hyperplastic, precancerous nodules. These results basically coincided with that of the separate observation of the expression of protooncogenes in the same study.
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PMID:[Expression of PCNA and protooncogenes during experimental hepatocarcinogenesis in rats]. 876 41

Recently, many inhibitors of farnesyl protein transferase (FPTase) have been identified. Some of them interrupt cell growth in addition to Ras and nuclear lamin processing of Ras-transformed cells. We have tested the effect of the FPTase inhibitors manumycin, an analogue of farnesyl diphosphate, and KT7595, a gliotoxin derivative, on Ras farnesylation, DNA synthesis and the anchorage-dependent and -independent growth of human colon carcinoma (LoVo), hepatoma (Mahlavu and PLC/PRF/5) and gastric carcinoma (KATO III). Both drugs severely inhibited DNA synthesis, cellular proliferation and Ras farnesylation in LoVo and moderately reduced them in Mahlavu and PLC/PRF/5 but not in KATO III. Complete sequencing of ras genes, however, revealed that LoVo and KATO III have activated Ki-ras and activated N-ras, respectively, whereas Mahlavu and PLC/PRF/5 have no activated ras. We next checked whether the inhibition of the cellular proliferation is due to the blocking of nuclear lamin function. Neither drug disturbed lamin farnesylation and localization, as demonstrated using metabolic labelling, immunoblotting and indirect immunofluorescence. These results indicate that manumycin and KT7595 can inhibit Ras farnesylation and cell growth without disturbing the farnesylation and localization of the lamins on human tumour cell lines.
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PMID:Manumycin and gliotoxin derivative KT7595 block Ras farnesylation and cell growth but do not disturb lamin farnesylation and localization in human tumour cells. 937 58

Several novel differentiated cell lines have been derived from a human hepatocarcinoma named HBG. Analysis of their functional properties evidenced a gradual differentiation process as they became confluent and a remarkable stability of the whole quiescent population for at least 6 weeks. However, when replated at low density after several weeks of quiescence, the differentiated cells were able to rapidly reverse to active proliferation, accompanied by transient dedifferentiation. Demonstration that the differentiated hepatic cells were growth-arrested in G1 phase was provided by the increased number of cells with 2C DNA content and decreased expression of S-phase markers. Characteristic features of oncogenes and cell cycle genes were defined during the differentiation process: (a) a biphasic expression of c-myc, with the latter wave covering the quiescence period; (b) opposite kinetics of c-Ki-ras and of N-ras expression with a pattern of changes paralleling that of c-myc; and (c) a decrease of cyclin D1 protein expression and of the cyclin D1-associated kinase activity. The mechanisms by which quiescent differentiated cells might reinitiate active proliferation were analyzed by studying several genes involved in cell growth and death regulation. We found: (a) a point mutation and loss of the specific activity of the tumor suppressor gene p53 without alteration of the apoptotic response to transforming growth factor beta1; (b) a gradual decrease of retinoblastoma protein, which was constantly present, mainly in a hyperphosphorylated form; and (c) an increase of cyclin-dependent kinase inhibitor p27 expression in confluent differentiating cells, as expected, whereas, surprisingly, a disappearance of the p21 protein was observed in parallel. These data may reflect specific mechanisms of cell cycle regulation in liver parenchymal cells through which these cells can proceed to control their reversible differentiation program.
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PMID:Cell cycle gene regulation in reversibly differentiated new human hepatoma cell lines. 948 53


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