Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma

Kobayashi, Yohnosuke; Higashi, Toshihiro; Nouso, Kazuhiro; Nakatsukasa, Harushige; Ishizaki, Masahiko; Kaneyoshi, Toshihiko; Toshikuni, Nobuyuki; Kariyama, Kazuya; Nakayama, Eiichi; Tsuji, Takao

doi:10.1016/s0168-8278(00)80223-8

Cited by 52 publications

(40 citation statements)

References 34 publications

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“…For example, GAGE expression in malignant melanomas was observed in 17% of specimens in our study, while a previous study showed that 30% of malignant melanomas were GAGE-1-8 mRNA-positive (Eichmuller et al, 2002). Similar differences were observed for lung carcinoma (16 vs 50%), thyroid carcinoma (10 vs 30%) and ovarian carcinoma (0 vs 30%) (Russo et al, 1996;De Backer et al, 1999;Ruschenburg et al, 1999;Kobayashi et al, 2000). Lower frequencies of tumours exhibiting MAGE-A1 and NY-ESO-1 staining, compared to previous mRNA-based studies, were also observed (Li et al, 1996;Zambon et al, 2001;Kong et al, 2004;Wang et al, 2004;Li et al, 2005).…”

Section: Discussionsupporting

confidence: 78%

“…Interestingly, expression of several CT antigens, including GAGE, can be induced by the hypomethylating agent 5-aza-2 0 -deoxycytidine (Sigalotti et al, 2002), and it has been shown that induction of transcription correlates with hypomethylation of CT antigen promoters (Janssen et al, 1999;De Smet et al, 2004). There also seem to be individual differences in the regulation of the transcription of GAGE genes since the GAGE members are not always co-expressed (Kobayashi et al, 2000;Eichmuller et al, 2002;Eichmuller et al, 2003).…”

mentioning

confidence: 99%

“…GAGE gene transcripts have been found in numerous types of cancers, most frequently in melanomas (De Backer et al, 1999;Eichmuller et al, 2002) and lung adenocarcinomas (De Backer et al, 1999), in which up to 54% of specimens were found to express GAGE, as well as in gastric cancers (Zambon et al, 2001;Kong et al, 2004) and hepatocellular carcinomas (Kobayashi et al, 2000).…”

mentioning

confidence: 99%

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Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

et al. 2006

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The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy.

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Section: Discussionsupporting

confidence: 78%

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confidence: 99%

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confidence: 99%

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Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

et al. 2006

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“…Despite improvement in sonographic examinations and therapy for HCC, the outcome generally remains unsatisfactory. Recently, the expression of CT antigen-encoding genes in HCC tissues has been reported by several laboratories (7)(8)(9)(10). Our own data have revealed that mRNA for at least 20 CT antigens can be detected in HCC tissues.…”

Section: Introductionmentioning

confidence: 60%

The Spontaneous CD8+ T-Cell Response to HLA-A2-Restricted NY-ESO-1b Peptide in Hepatocellular Carcinoma Patients

Shang

Chen²,

Zhang

et al. 2004

Clinical Cancer Research

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“…Kip1 (Tannapfel et al, 2000), p16 INK4 , cyclin D1, and cyclin E (Jung et al, 2001), pRb2/p130 (Huynh, 2004), SAP-1 (Nagano et al, 2003), PIN1 (Pang et al, 2004), LFIRE-1/HFREP-1 (Yan et al, 2004), MXR-7 (Hsu et al, 1997), and MAGE (Kobayashi et al, 2000). Many of them are involved in cell cycle checkpoint control; thus, the deregulation of these genes is likely to contribute to the tumor progression.…”

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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Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma

Cited by 52 publications

References 34 publications

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy

The Spontaneous CD8+ T-Cell Response to HLA-A2-Restricted NY-ESO-1b Peptide in Hepatocellular Carcinoma Patients

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

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