Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma

Osaki, Mitsuhiko; Moriyama, Masatsugu; Adachi, Keiko; Nakada, Chisato; Takeda, Ami; Inoue, Yasuhiro; Adachi, Hisashi; Sato, Kei; Oshimura, Mitsuo; Ito, Hisao

doi:10.1111/j.1365-2362.2004.01401.x

Cited by 37 publications

(54 citation statements)

References 26 publications

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“…Specifically, no G-cells in the antral mucosa showed any RUNX3 expression (Figure 3a), despite a recent report that RUNX3 is expressed in a subset of normal gastric epithelial cells, notably in chief cells of fundic glands and in G-cells located in the pyloric portion of the normal stomach (Osaki et al, 2004). Furthermore, we observed nuclear RUNX3 staining in some tumour cells (Table 2, Figure 4b).…”

Section: Discussioncontrasting

confidence: 46%

“…These observations were linked with the discovery of RUNX3 silencing in about 60% of human gastric cancer specimens analysed (Li et al, 2002). These results led to several studies being published where the loss of RUNX3 appeared as an important event in gastric carcinogenesis (Ito and Miyazono, 2003;Bae and Choi, 2004;Fukamachi and Ito, 2004;Osaki et al, 2004). Brenner et al (2004), on the other hand, reported that, at E4 weeks of age, Runx3 À/À mice (with a heterogeneous ICR and MF1 genetic background) developed colitis and only at an older age (E8 months) went on to develop gastric mucosal hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

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Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas

et al. 2005

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Recent studies claim a critical role for RUNX3 in gastric epithelial homeostasis. However, conflicting results exist regarding RUNX3 expression in the stomach and its potential role as a tumour-suppressor gene (TSG) in gastric carcinogenesis. Our aim was to evaluate the role of RUNX3 in early-onset gastric carcinomas (EOGCs). We analysed 41 EOGCs for RUNX3 aberrations using loss of heterozygosity (LOH), fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) analyses. LOH of markers flanking RUNX3 was relatively common, indicating that loss of the gene may play a role in gastric carcinogenesis. However, FISH analysis of selected cases and a panel of 14 gastric carcinoma-derived cell lines showed widespread presence of multiple copies of centromere 1. While RUNX3 copy numbers were generally equal to or fewer than those of centromere 1, at least two copies were present in almost all cells analysed. Accordingly, a subpopulation of tumour cells in 12/37 cases showed RUNX3 protein expression. However, expression was not detected in the adjacent nontumorous mucosa of any case. Together, these observations indicate that chromosome 1 aberrations occur frequently in EOGCs and are reflected in the LOH and IHC patterns found. Our findings refute a role for RUNX3 as a TSG in EOGCs.

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Section: Discussioncontrasting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas

et al. 2005

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“…11 However, the role of RUNX3 as a possible gastric tumor suppressor is yet controversial. 7,12,[14][15][16] Moreover, the results of present study are not consistent with those of the previous reports in that the positive MSP expression of the RUNX3 gene was found only in 32.9% of the patients, which is relatively lower than those of the previous reports (45-69%), 7,8 including the Korean-specific data (56-64%). 11,12 RUNX3-specific methylation was more frequently identified in the gastric carcinoma specimens (32.9%) than in the nonneoplastic mucosa (11.4%), although marginally significant (p=0.053).…”

Section: Discussioncontrasting

confidence: 57%

“…12 In addition, methylation of the multiple tumor suppressor genes including RUNX3 were found to increase with age in the nonneoplastic gastric epithelia. 13 Although the absence of RUNX3 expression has been reported in several studies on the human gastric carcinoma, 7,11,12,14,15 a recent study reported that the immunohistochemical staining detected the RUNX3 protein expression in the infiltrating leukocytes, but not in the gastric epithelium. 16 Therefore, the low levels of RUNX3 expression in the gastric epithelium and the absence of downregulation of RUNX3 in the gastric cancer do not support the idea that RUNX3 functions as a gastric tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 99%

Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma

Song

Shim²,

Joo³

et al. 2008

Gut Liver

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Background/Aims: RUNX3 (PEBP2αC/CBFA3/AML2) is a novel tumor suppressor gene in the human gastric carcinoma. The aims of this study were to determine the methylation of RUNX3 promoter and the association between RUNX3 methylation and the clinicopathological characteristics of patients with gastric carcinoma. Methods: Seventy-nine patients with gastric carcinoma were studied prospectively from April 2005 to May 2007. The methylations of RUNX3 promoter on the gastric carcinoma specimens and the corresponding nonneoplastic mucosa were evaluated by methylation-specific polymerase chain reaction. Results: Comparison of the results with the clinicopathological characteristics identified RUNX3 monoallelic methylation in 32.9% (26/79) of the gastric carcinoma patients and in 11.4% (9/79) of those with nonneoplastic mucosa (p=0.053). The monoallelic methylated gastric carcinoma specimens predominantly consisted of well-and moderately differentiated carcinomas (44.7%), with the unmethylated group constituting 22.0% of them (p=0.031). Among the 48 patients (60.8%) who underwent gastrectomy, there was no correlation between the two groups with regard to Lauren's classification (p=0.235), depth of invasion (p=0.990), nodal status (p=0.601), stage (p=0.900), lymphatic invasion (p=0.537), and vascular invasion (p=0.815). Conclusions: Methylation of the tumor suppressor gene RUNX3 might be one of the mechanisms involved in the pathogenesis of gastric carcinoma. (Gut and Liver 2008;2:119-125)

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“…A mutation of Arg122 to Cys in the conserved Runt domain abolished the tumor-suppressive effect of RUNX3 (Li et al, 2002). Several other groups have also demonstrated the expression of RUNX3 mRNA and/or protein in gastric epithelial cells (Osaki et al, 2004;Oshimo et al, 2004;Torquati et al, 2004;Wei et al, 2005;Zavros et al, 2005;Katuri et al, 2006;Peng et al, 2006;Usui et al, 2006). However, others have failed to demonstrate the expression of Runx3 in normal gastric epithelial cells immunohistochemically using G-poly and this has led them to question its contribution to carcinogenesis in GIT epithelium (Levanon et al, 2001(Levanon et al, , 2003Brenner et al, 2004, Carvalho et al, 2005.…”

mentioning

confidence: 99%

Runx3 expression in gastrointestinal tract epithelium: resolving the controversy

Ito

Inoue

et al. 2009

Oncogene

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We reported earlier that RUNX3 is expressed in human and mouse gastrointestinal tract (GIT) epithelium and that it functions as a tumor suppressor in gastric and colorectal tissues. However, there have been conflicting reports describing the absence of Runx3 in GIT epithelial cells. A part of the controversy may be derived from the use of a specific antibody by other groups (referred to as G-poly). Here, we show further evidence to support our earlier observations and provide a possible explanation for this apparent controversy. We generated multiple anti-RUNX3 monoclonal antibodies and found that RUNX3 antibodies recognizing the RUNX3 N-terminal region (residues 1-234) react with RUNX3 in gastric epithelial cells, whereas those recognizing the C-terminal region (beyond residue 234) did not. G-poly primarily recognizes the region beyond 234 and hence, is unable to detect Runx3 in this tissue.

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Expression of RUNX3 protein in human gastric mucosa, intestinal metaplasia and carcinoma

Abstract: These data suggest that RUNX3 may play a physiologic role in chief cells and G cells in gastric mucosa, and that suppression of RUNX3 expression in intestinal metaplasia and carcinoma of human stomach may be implicated in gastric carcinogenesis.

Cited by 37 publications

References 26 publications

Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas

Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas

Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma

Runx3 expression in gastrointestinal tract epithelium: resolving the controversy

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