Distinct Expression ofCDX2 andGATA4/5, Development-Related Genes, in Human Gastric Cancer Cell Lines

Bai, Yun-Qing; Akiyama, Yoshimitsu; Nagasaki, Hiromi; Yagi, Osmar Kenji; Kikuchi, Yoko; Saito, Naoya; Takeshita, Kimiya; Iwai, Takehisa; Yuasa, Yasuhito

doi:10.1002/1098-2744(200007)28:3<184::aid-mc7>3.0.co;2-6

Cited by 48 publications

(40 citation statements)

References 23 publications

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“…Consistent with published reports (Bai et al, 2000), CDX2 was minimally expressed in normal human stomach, upregulated in stomach cancer tissue, and moderately expressed in MKN45 cells. Thus, the level of CDX2 expression in MKN45 cells is comparable to levels seen in gastric cancer tissues, other gastric cancer cell lines, and some colon cancer cell lines.…”

Section: Expression and Genetic Analysis Of Cdx2supporting

confidence: 91%

“…We reasoned that it was important to target the disruption in MKN45 gastric cancer cells rather than colon cancer cells, as CDX2 functions in a cell type-specific manner. Furthermore, the level of CDX2 expression may affect its function, and CDX2 expression in MKN45 cells is most consistent with levels found in primary gastric cancers and cell lines (Bai et al, 2000) (Figure 1a). Finally, MKN45 cells have been shown to be near diploid, stable over long periods in culture, and consistent with a tubular adenocarcinoma histology (Motoyama et al, 1986).…”

Section: Expression and Genetic Analysis Of Cdx2supporting

confidence: 78%

“…In a comparison study between normal gastric epithelium and 11 human gastric cancer cell lines, MKN45 was found to express moderate amounts of CDX2 by reverse transcription (RT)-PCR analyses (Bai et al, 2000). In the same study, the expression of GATA 4/5 transcription factors was associated with CDX2 expression in MKN45 cells.…”

Section: Expression and Genetic Analysis Of Cdx2mentioning

confidence: 91%

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CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45

et al. 2005

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CDX2 is a Drosophila caudal-related homeobox transcription factor that is expressed specifically in the intestine. In mice, ectopic expression of CDX2 in the gastric mucosa gives rise to intestinal metaplasia and in one model, gastric carcinoma. In humans, increased CDX2 expression is associated with gastric intestinal metaplasia and tubular adenocarcinomas. These patterns of expression have shown that CDX2 is important for the initiation of intestinal metaplasia in the gastric mucosa, but the role of CDX2 in established gastric cancer remains unclear. We sought to determine whether CDX2 contributes to tumorigenic potential in established gastric cancer. The CDX2 gene in MKN45 gastric carcinoma cells was disrupted using targeted homologous recombination. The resulting CDX2 À/À cells are essentially identical to their parental cells, with the exception of CDX2 ablation. We found no significant differences in the proliferation of CDX2 À/À cells compared to CDX2þ / þ cells, in vitro or in vivo. Molecular analyses show that loss of CDX2 predominantly altered the expression of genes involved in intestinal glandular differentiation and adhesion. However, there were no microscopic differences in tumor differentiation. We conclude that disruption of CDX2 in MKN45 cells does not significantly affect their tumorigenic potential.

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Section: Expression and Genetic Analysis Of Cdx2supporting

confidence: 91%

Section: Expression and Genetic Analysis Of Cdx2supporting

confidence: 78%

Section: Expression and Genetic Analysis Of Cdx2mentioning

confidence: 91%

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CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45

et al. 2005

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“…31 In conclusion, down-regulation of GATA-3 was correlated with HPV-mediated immortalization in vitro and advanced (pre)malignant cervical disease. Therefore, it may provide a marker for progressive CIN disease.…”

Section: Discussionmentioning

confidence: 88%

Down-Regulation of GATA-3 Expression during Human Papillomavirus-Mediated Immortalization and Cervical Carcinogenesis

Steenbergen

OudeEngberink

Kramer

et al. 2002

The American Journal of Pathology

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To identify cellular genes that may be involved in human papillomavirus (HPV)-mediated immortalization mRNA differential display analysis was performed on preimmortal and subsequent immortal stages of four human keratinocyte cell lines transformed by HPV type 16 or 18 DNA. This yielded a cDNA fragment encoding the transcription factor GATA-3 that was strongly reduced in intensity in all immortal stages of the four cell lines. A marked reduction in both GATA-3 mRNA and protein expression in HPV-immortalized cell lines was confirmed by reverse transcriptase-polymerase chain reaction, Western blot analysis, and immunohistochemistry and was also shown to be apparent in cervical carcinoma cell lines. Immunohistochemical analysis of cervical tissue specimens showed a clear nuclear staining for GATA-3 in normal cervical squamous epithelium (n ‫؍‬ 14) and all cervical intraepithelial neoplasia (CIN) I (n ‫؍‬ 6) and CIN II lesions (n ‫؍‬ 2). In contrast, 11% (1 of 9) of CIN III lesions and 67% (8 of 12) of cervical squamous cell carcinomas revealed a complete absence of GATA-3 immunostaining. Hence, complete down-regulation of GATA-3 expression represents a rather late event during cervical carcinogenesis. Whether GATA-3 down-regulation is etiologically involved in HPV-mediated immortalization and cervical carcinogenesis remains to be examined. Infection with high-risk human papillomavirus (HPV) types is the most significant risk factor for the development of cervical cancer and HPV DNA can be detected in almost all cervical squamous cell carcinomas. 1 HPV functions are, however, not sufficient for the development of cervical cancer and additive oncogenic events involving host cell genes are required, consistent with a multistep process of carcinogenesis. To gain better insight in HPV-mediated carcinogenesis in vitro model systems have been proven very valuable. High-risk HPV types, in particular HPV 16 and HPV 18, can induce immortalization of primary human epithelial cells in vitro. [2][3][4] Studies involving somatic cell fusions and microcell-mediated chromosome transfers have indicated that particularly recessive gene alterations are crucial for immortalization of HPV-containing epithelial cells. 5,6 HPV-mediated immortalization is associated with an arrest of telomeric shortening and activation of the telomere lengthening enzyme telomerase. 4,7 Moreover, activation of telomerase, by up-regulation of its catalytic subunit human telomerase reverse transcriptase gene, seemed to be necessary and sufficient for immortalization of HPV-transfected keratinocytes. 6,8,9 In addition, expression of the viral oncogene HPV 16 E6 from a heterologous promoter has been shown to activate telomerase in primary keratinocytes. 10 However, expression of HPV 16 and HPV 18 E6 from their native promoter in the context of the fulllength virus genome did not result in telomerase activation, 4 indicating that additive events are required.Recent studies have shown that yet unknown genes residing at chromosomes 3, 4, and 6 can regulate telomer...

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“…CDX2 decreases along gastric carcinogenesis Q Liu et al observed that stronger CDX2 expression was associated with better differentiation of gastric cancer tissues [28][29][30]32 and cell lines. 39 Further decrease of CDX2 in incomplete IM may lead to a less differentiated state and more instability. This scenario may explain the observed progressive decrease of CDX2 from incomplete IM to dysplasia to cancer.…”

Section: Discussionmentioning

confidence: 99%

CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer

et al. 2007

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Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer.

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Distinct Expression ofCDX2 andGATA4/5, Development-Related Genes, in Human Gastric Cancer Cell Lines

Cited by 48 publications

References 23 publications

CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45

CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45

Down-Regulation of GATA-3 Expression during Human Papillomavirus-Mediated Immortalization and Cervical Carcinogenesis

CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer

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