Expression of MAGE Genes in Human Colorectal Carcinoma

Mori, Masaki; Inoue, Hiroshi; Mimori, Koshi; Shibuta, Kenji; Baba, Kanji; Nakashima, Hiroaki; Haraguchi, Masanobu; Tsuji, K.; Ueo, Hiroaki; Barnard, Graham F.; Akiyoshi, Tsuyoshi

doi:10.1097/00000658-199608000-00011

Cited by 67 publications

(57 citation statements)

References 24 publications

(1 reference statement)

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“…For our investigations, we chose besides breast and prostate cancer cell lines different MAGE-negative cell lines HL60, Colo205, WiDr, and HepG2, whose MAGE-A gene expression has been shown not to be inducible despite extensive treatment with 5-aza-CdR (16)(17)(18)(19). In all cell lines tested with the exception of HepG2 cells, we were able to stimulate MAGE-A expression with the demethylating agent.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that both DNA hypermethylation and hypomethylation play a crucial role during tumorigenesis, and transcriptional activation might be induced by promoter demethylation. However, several laboratories have shown that although tumor cells were treated by the DNA methylase inhibitor 5-aza-2 ¶-deoxycytidine (5-aza-CdR) up-regulation of MAGE-A gene expression could not be always observed (2,(16)(17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

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Promoter Demethylation and Histone Acetylation Mediate Gene Expression of MAGE-A1, -A2, -A3, and -A12 in Human Cancer Cells

Wischnewski

Pantel

Schwarzenbach

2006

Molecular Cancer Research

159

123

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The broad range of expression of cancer-testis antigens in various tumor types makes the proteins encoded by human MAGE gene family promising targets for anticancer immunotherapy. However, a major drawback is their heterogeneous expression. In the current study, we have examined the influence of the DNA methylase inhibitor 5-aza-2 ¶-deoxycytidine (5-aza-CdR) together with the histone deacetylase inhibitor trichostatin A on the expression of MAGE-A1, -A2, -A3, and -A12 genes in different cell lines. Reverse transcription-PCR, Western blot analyses, and immunocytochemical staining show that trichostatin A was able to significantly up-regulate 5-aza-CdR-induced MAGE gene expression. Transient transfection assays with methylated reporter plasmids containing promoter fragments of the different MAGE genes show that trichostatin A was able to overcome gene silencing. In addition, the methylation status of the MAGE promoters was assessed by sodium bisulfite mapping in the various cell lines before and after stimulation with 5-aza-CdR and/or trichostatin A. In contrast to the methylation patterns, which clearly correlated with the basal MAGE RNA transcripts, up-regulation of the MAGE-A mediated by both agents only resulted in a reduction in promoter methylation ranging between 1% and 19%. In conclusion, our data show for the first time that not only hypermethylation but also histone deacetylation is responsible for the mechanism underlying MAGE gene silencing.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Promoter Demethylation and Histone Acetylation Mediate Gene Expression of MAGE-A1, -A2, -A3, and -A12 in Human Cancer Cells

Wischnewski

Pantel

Schwarzenbach

2006

Molecular Cancer Research

159

123

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“…To evaluate the methylation status of the promoter region of GNG7 in oesophageal cancer, cell lines were treated with a demethylating drug, 5-AZAC, as in our previous study (Mori et al, 1996). We analysed GNG7 expression by quantitative RT-PCR before and after 5-AZAC treatment in 15 oesophageal cancer cell lines.…”

Section: -Azac Treatment Of Oesophageal Cancer Cell Linesmentioning

confidence: 99%

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

et al. 2008

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We previously cloned human G protein gamma 7 (GNG7) and demonstrated that it was downregulated in gastrointestinal cancer. The significance of GNG7 expression in oesophageal cancer is unknown. TaqMan quantitative real-time PCR was performed to determine the clinical significance of GNG7 expression in 55 cases of oesophageal cancer. Furthermore, GNG7-transfected oesophageal cancer cells were analysed in laboratory studies at genomic and epigenetic levels. Twenty-seven patients with low GNG7 expression showed significantly poorer survival than did 28 patients with high expression (Po0.05). Tumours with low GNG7 expression invaded deeper than those with high GNG7 expression (Po0.05), both in vivo and in vitro. Eight tumours retained GNG7 expression, and they did not show either promoter hypermethylation or loss of heterozygosity (LOH). In 38 tumours with GNG7 suppression, 22 (57%) showed either LOH or promoter hypermethylation. In addition, GNG7 expression was significantly associated with the presence of miR328 in oesophageal cancer cell lines, which suggests that this microRNA might be a regulator of GNG7 expression. GNG7 suppression represents a new prognostic indicator in cases of oesophageal cancer. GNG7 might be suppressed by LOH and promoter hypermethylation or by microRNA.

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“…We previously reported that MAGE-1 and MAGE-3 genes were expressed in 62% and 57% of oesophageal carcinomas (Inoue et al, 1997), 41% and 38% of gastric carcinomas (Inoue et al, 1995), 30% and 20% of colorectal carcinomas (Mori et al, 1996), 24% and 31% of breast carcinomas , and more than 65% of hepatocellular carcinomas . We also identified some MAGE gene-encoded peptides recognized by CTL Fujie et al, 1999).…”

Section: Introductionmentioning

confidence: 95%

Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas

et al. 2001

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Summary Cancer-testis antigens (CTAs) such as MAGE are selectively expressed in various types of human neoplasms but not in normal tissues other than testis. This characteristic feature of CTAs makes them promising antigens for cancer-specific immunotherapy. A critical requirement for this therapy is identification of promising antigens. In this study, we investigated the expression of 6 genes recently identified by serological analysis of antigens by recombinant expression (SEREX) libraries: NY-ESO-1, LAGE-1, SCP-1, SSX-1, SSX-2, and SSX-4, in many surgical samples of gastrointestinal and breast carcinomas using reverse transcription-polymerase chain reaction. We found relatively high expression of SCP-1 (23.5%) and SSX-4 (20.6%) in gastric carcinoma, LAGE-1 (39.1%) and NY-ESO-1 (23.9%) in oesophageal carcinoma, and SCP-1 (34.1%) in breast carcinoma. We also found frequent synchronous expression with MAGE, including LAGE-1 (46.2%) in oesophageal carcinoma, SSX-4 (46.7%) in gastric carcinoma, and SCP-1 (38.3%) in breast carcinoma. Immunohistochemical analysis of the tumour samples expressing both MAGE-4 and NY-ESO-1 genes demonstrated differences in distribution between MAGE-4 and NY-ESO-1 in serial sections. We concluded that NY-ESO-1, LAGE-1, SCP-1 and SSX-4 genes may be promising candidates for cancer-specific immunotherapy in addition to MAGE, and that polyvalent cancer vaccines may be useful in cases of heterogeneous expressions of CTA genes in gastrointestinal and breast carcinomas.

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Expression of MAGE Genes in Human Colorectal Carcinoma

Cited by 67 publications

References 24 publications

Promoter Demethylation and Histone Acetylation Mediate Gene Expression of MAGE-A1, -A2, -A3, and -A12 in Human Cancer Cells

Promoter Demethylation and Histone Acetylation Mediate Gene Expression of MAGE-A1, -A2, -A3, and -A12 in Human Cancer Cells

Clinical significance of the reduced expression of G protein gamma 7 (GNG7) in oesophageal cancer

Expression of multiple cancer-testis antigen genes in gastrointestinal and breast carcinomas

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