Point mutation, allelic loss and increased methylation of c-Ha-ras gene in human hepatocellular carcinoma

Ogata, Naoki

doi:10.1016/0270-9139(91)90212-e

Cited by 9 publications

(10 citation statements)

References 14 publications

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“…HCC development is a multistep process and a consequence of accumulation of genetic abnormalities, which facilitate cell transformation (Hanahan and Weinberg, 2000). Although the molecular mechanism of hepatocarcinogenesis remains unclear, the genetic lesions in oncogenes, such as ras (Ogata et al, 1991), c-myc (Kawate et al, 1999), and tumor suppressors, such as p53 (Nishida et al, 1993;Tanaka et al, 1993;Rashid et al, 1999) and Rb (Murakami et al, 1991;Buendia, 2000;Suriawinata and Xu, 2004), have been identified in HCC. Moreover, accumulated evidence shows that over 20 cellular genes are up-or downregulated in HCC.…”

Section: Introductionmentioning

confidence: 99%

DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control

Chang¹,

Chi²,

et al. 2005

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and is highly correlated with hepatitis virus infection. Our previous report shows that a DEAD box RNA helicase, DDX3, is targeted and regulated by hepatitis C virus (HCV) core protein, which implicates the involvement of DDX3 in HCV-related HCC development. In this study, the potential role of DDX3 in hepatocarcinogenesis is investigated by examining its expression in surgically excised human HCC specimens. Here we report the differential deregulation of DDX3 expression in hepatitis virus-associated HCC. A significant downregulation of DDX3 expression is found in HCCs from hepatitis B virus (HBV)-positive patients, but not from HCV-positive ones, compared to the corresponding nontumor tissues. The expression of DDX3 is differentially regulated by the gender and, moreover, there is a tendency that the downregulation of DDX3 expression in HCCs is more frequent in males than in females. Genetic knockdown of DDX3 with small interfering RNAs (siRNA) in a nontransformed mouse fibroblast cell line, NIH-3T3, results in a premature entry to S phase and an enhancement of cell growth. This enhanced cell cycle progression is linked to the upregulation of cyclin D1 and the downregulation of p21 WAF1 in the DDX3 knockdown cells. In addition, constitutive reduction of DDX3 expression increases the resistance of NIH-3T3 cells to serum depletion-induced apoptosis and enhances the ras-induced anchorage-independent growth, indicating the involvement of DDX3 in cell growth control. These findings together with the previous study suggest that the deregulation of DDX3, a DEAD box RNA helicase with cell growth-regulatory functions, is involved in HBV-and HCV-associated pathogenesis.

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Section: Introductionmentioning

confidence: 99%

DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control

Chang¹,

Chi²,

et al. 2005

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“…The multiple hepatocarcinogenesis involves large molecular events including genetic and epigenetic changes, which accumulate through progression (Hui and Makuuchi, 1999;Zimmermann et al, 1997). The genetic deviation encompasses DNA rearrangements associated with viral genome integration (Zondervan et al, 2000), point mutations (Ogata et al, 1991;Shimizu et al, 1999;de La Coste et al, 1998), loss of heterozygosity (Teeguarden et al, 2000;Kondo et al, 2000), chromosomal amplifications (Kawate et al, 1999), changes in methylation (Kondo et al, 2000;Shen et al, 1998), translocations (Keck et al, 1999), and gain or loss of imprinting (de Souza et al, 1997;Schwienbacher et al, 2000). These changes could occur in a variety of cellular genes leading to escape from normal cellular and environmental controls.…”

Section: Introductionmentioning

confidence: 99%

“…These changes could occur in a variety of cellular genes leading to escape from normal cellular and environmental controls. So far, over 20 cellular genes down-or up-regulated or mutated in HCC such as ras (Ogata et al, 1991;Kim et al, 2001), c-myc, c-fos, and c-jun (Kawate et al, 1999;Yuen, et al, 2001), rho (Genda et al, 1999), TGFa (Chung et al, 2000), HGF and c-met (Ueki et al, 1997), c-erbB-2 (Collier et al, 1992), IGF-II (Takeda et al, 1996), u-PA (de Petro et al, 1998), MXR7 (Hsu et al, 1997), MDM2 (Endo et al, 2000), MAGE (Tahara et al, 1999), matrix metalloproteinase (Musso et al, 1997), Smads (Yakicier et al, 1999), p53 (Shimizu et al, 1999;Rashid et al, 1999), pRB Santoni-Rugiu et al, 1998), p16INK4 Liew et al, 1999), p21 WAF1/CIP1 , p27 Kip1 (Chen et al, 2000;Tannapfel et al, 2000), PTEN (Fujiwara et al, 2000;Yao et al, 1999), E-cadherin ), beta-catenin (de La Coste et al, 1998 and AXIN1 (Satoh et al, 2000) have been described in humans and mice. Many of them are involved in deregulation of intracellular signal transduction and cell cycle, leading eventually to an uncontrolled proliferation of cancerous cells.…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma

et al. 2002

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To gain new insight into the molecular mechanism underlying the pathogenesis of human primary hepatocellular carcinoma (HCC), we searched for HCC-specific molecules through screening genes that are differentially expressed between cancerous and noncancerous counterparts of liver and identified a novel HCC-associated gene, HCCA1 encoding a *80 kDa cytoplasmic protein that contains several proline-rich motifs likely for SH3-binding. HCCA1 transcript, albeit present in some adult tissues, is up-regulated selectively in HCC but not in other tumor cells. High expression of HCCA1 occurs as a late event frequently (89.2%) in HCCs and correlated significantly with the degree of tumor progression. When treated with antisense oligonucleotides to HCCA1, HCCA1 expression in HCC cells (HuH-7) was effectively suppressed and cell growth was down-regulated in a time-and dose-dependent manner. Furthermore, HuH-7 cells harboring the HCCA1 antisense expression clone displayed a remarkably reduced efficiency in colony formation. Together, these data strongly suggest that HCCA1 is a positive effector in cell proliferation and contributes to HCC carcinogenesis and progression. We believe that this protein will serve as a novel useful marker for HCC and is a potential target for pharmaceutical intervention of this malignant disease.

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“…Serum DNA was extracted by a sodium hydroxide procedure (16). Liver tissue DNA was extracted essentially as described (17,18). Serum (10 ,ul) or :1 mm3 of the liver tissue was used for the reaction.…”

mentioning

confidence: 99%

Markedly prolonged incubation period of hepatitis B in a chimpanzee passively immunized with a human monoclonal antibody to the a determinant of hepatitis B surface antigen.

Ogata

Östberg

Ehrlich

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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The protective efficacy of a human monoclonal antibody directed against the a determinant of hepatitis B virus (HBV) surface antigen was studied in a chimpanzee. A single high dose of 5 mg/kg (body weight) of monoclonal antibody SDZ OST 577 was intravenously administered to a chimpanzee, followed by intravenous challenge with 103-5 chimpanzee infectious doses of a wild-type HBV, the MS-2 strain (ayw subtype). The passively acquired antibody to HBV surface antigen could be detected for 40 weeks. Serum HBV DNA tested by a "nested" polymerase chain reaction assay was negative through the 36th week after virus challenge but became positive by the 38th week. The chimpanzee subsequently developed acute hepatitis B -1 year after challenge. The nucleotide sequence of the a determinant of the surface gene of the replicated virus was identical with that of the inoculated wild-type virus. Thus, a human monoclonal antibody directed against the a determinant ofHBV surface antigen delayed but did not prevent experimental infection of HBV and hepatitis in the chimpanzee. Our results indicate an incomplete ability of this antibody to protect against HBV infection in vivo after a single infusion.

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Point mutation, allelic loss and increased methylation of c-Ha-ras gene in human hepatocellular carcinoma

Cited by 9 publications

References 14 publications

DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control

DDX3, a DEAD box RNA helicase, is deregulated in hepatitis virus-associated hepatocellular carcinoma and is involved in cell growth control

Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma

Markedly prolonged incubation period of hepatitis B in a chimpanzee passively immunized with a human monoclonal antibody to the a determinant of hepatitis B surface antigen.

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