Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CDX2 is a tumor-suppressor homeobox gene involved in colon carcinogenesis, but its role in gastric cancer is unknown. Although GATA4, -5 and, -6 transcription factors have distinct functions in the regulation of gastrointestinal epithelial cell differentiation, there have been no reports regarding GATA4/5/6 alterations in gastrointestinal carcinomas. By using a semiquantitative reverse transcription-polymerase chain reaction assay, we studied the expression of gut development-related genes CDX2/1 and GATA4/5/6 in 11 human gastric cancer cell lines. The expression of CDX2 appeared to progressively decrease with the transition from well differentiated to poorly differentiated cancer cell lines. CDX1 was below detectable levels in all cell lines. The expression of GATA4 and GATA5 was undetectable in four and six cell lines, respectively, whereas the majority of the cell lines expressed GATA6 abundantly. These results suggest that CDX2 and GATA4/5 may be associated with the carcinogenesis of the stomach. Mol. Carcinog. 28:184-188, 2000.
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PMID:Distinct expression of CDX2 and GATA4/5, development-related genes, in human gastric cancer cell lines. 1094 35

CDX2, a transcriptional factor expressed in the intestine, is implicated in the development and maintenance of the intestinal mucosa. Recent studies have demonstrated that CDX2 is expressed in the intestinal metaplasia of the stomach and intestinal-type gastric cancer, while it is not expressed in the normal gastric mucosa. To investigate the role of CDX2 in gastric cancer, we determined CDX2 expression and cell proliferation rate in various types of gastric cancer tissues by immunostaining. Surgically dissected gastric cancer tissues were collected from 40 patients. Consistent with previous reports, CDX2 was expressed in most gastric mucosa samples with intestinal metaplasia (89%, 16/18), although it was not found in the adjacent normal mucosa. CDX2 expression was also detected in 64% (18/28) of intestinal-type gastric cancer cases, whereas it was not observed in the diffuse-type gastric cancer (0/12). Moreover, the CDX2-positive gastric cancer samples showed significantly lower index for Ki-67 immunostaining, indicating reduced cell proliferation rates than in the CDX2-negative samples. Importantly, multivariate analysis for the overall survival rate revealed that the CDX2-positive gastric cancer patients survived significantly longer than the CDX2-negative patients. Even among the intestinal-type gastric cancer cases, the CDX2-positive group showed a lower Ki-67 index and longer postoperative survival than the CDX2-negative group. These results collectively indicate that CDX2 expression in gastric cancer tissues can be a novel prognostic marker for patient survival.
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PMID:CDX2 expression in the stomach with intestinal metaplasia and intestinal-type cancer: Prognostic implications. 1223 15

Intestinal metaplasia (IM) is part of a stepwise sequence of alterations of the gastric mucosa, leading ultimately to gastric cancer, and is strongly associated with chronic Helicobacter pylori infection. The molecular mechanisms underlying the onset of IM remain elusive. The aim of this study was to assess the putative involvement of two intestine-specific transcription factors, CDX1 and CDX2, in the pathogenesis of gastric IM and gastric carcinoma. Eighteen foci of IM and 46 cases of gastric carcinoma were evaluated by immunohistochemistry for CDX1 and CDX2 expression. CDX1 was expressed in all foci of IM and in 41% of gastric carcinomas; CDX2 was expressed in 17/18 foci of IM and in 54% of gastric carcinomas. In gastric carcinomas, a strong association was observed between the expression of CDX1 and CDX2, as well as between the intestinal mucin MUC2 and CDX1 and CDX2. No association was observed between the expression of CDX1 and CDX2 and the histological type of gastric carcinoma. In conclusion, these results show that aberrant expression of CDX1 and CDX2 is consistently observed in IM and in a subset of gastric carcinomas. The association of CDX1 and CDX2 with expression of the intestinal mucin MUC2, both in IM and in gastric carcinoma, indirectly implies that CDX1 and CDX2 may be involved in intestinal differentiation along the gastric carcinogenesis pathway.
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PMID:Expression of intestine-specific transcription factors, CDX1 and CDX2, in intestinal metaplasia and gastric carcinomas. 1247 24

Epigenetic gene silencing through DNA methylation is one of the important steps in the mechanism underlying tumorigenesis, including in the stomach. Past lifestyle factors of cancer patients, such as intake of vegetables, are very important in affecting gastric carcinogenesis. However, the relationship between DNA methylation and past dietary habits in cancer patients remains largely unknown. The CDX2 homeobox transcription factor plays a key role in intestinal development, but CDX2 is also expressed in most of the intestinal metaplasia and part of the carcinomas of the stomach. We analyzed the methylation status of the CDX2 5' CpG island in gastric cancer cell lines by methylation-specific PCR (MSP), and then CDX2 mRNA was found to be activated after 5-aza-2'-deoxycytidine treatment of the methylation-positive cells. We further examined the methylation status of CDX2 in primary gastric carcinomas by MSP and compared it with the past lifestyle of the patients, including dietary habits. Methylation of CDX2 was found in 20 (34.5%) of the 58 male patients and one (6.7%) of the 15 female patients. Since the methylation frequency was low in the female patients, the analysis was performed only on the male cases. CDX2 methylation was correlated with the decreased intake of green tea and cruciferous vegetables, and also with full or overeating habits. These findings are consistent with epidemiological observations on gastric cancer. We also analyzed the methylation status of p16/INK4a and hMLH1, but their frequencies were not associated with dietary factors or other lifestyle factors. Thus, diet could be an important factor determining the methylation status of genes such as CDX2 and the resultant aberrant expression of genes involved in carcinogenesis.
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PMID:Relationship between CDX2 gene methylation and dietary factors in gastric cancer patients. 1549 92

CDX2 and liver-intestine (LI)-cadherin are intestine-specific markers and both are physiologically expressed in the small intestine and colon. Recent studies have demonstrated that CDX2 regulates LI-cadherin gene (CDH17) expression in colorectal cancer. The present study investigated the relationship of CDX2 and LI-cadherin expression in gastric cancer. One hundred and nine pairs of tumour and non-cancerous gastric mucosa were collected from gastrectomy specimens. Protein expression levels of CDX2 and LI-cadherin were determined by immunohistochemical staining. Semi-quantitative RT-PCR showed that the mRNAs of both CDX2 and CDH17 were highly expressed in tumour compared with non-cancerous mucosa. Overexpression of CDX2 was significantly associated with CDH17 in gastric adenocarcinoma. Furthermore, the expression of CDX2 and LI-cadherin proteins was strongly coupled in intestinal metaplasia. In conclusion, overexpression of CDH17 is significantly associated with CDX2.
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PMID:CDX2 co-localizes with liver-intestine cadherin in intestinal metaplasia and adenocarcinoma of the stomach. 1573 40

Certain pulmonary adenocarcinomas show gastrointestinal differentiation with the expression of various mucins. The CDX homeobox gene, an intestine-specific transcription factor, is related to gastric carcinogenesis with MUC2 and MUC6 expression. The intestinal mucin MUC2 is expressed in the normal lung, while the gastric mucin MUC6 is not. Previously, we have reported that the expressions of MUC2 and MUC6 were related to a poor prognosis in small adenocarcinomas of the lung. We estimated the expressions of the mucin (MUC2 and MUC6) and CDX (CDX1 and CDX2) to examine how CDX relates to the gastrointestinal mucin production in the pulmonary adenocarcinoma. Thirty-nine human non-small cell lung cancer (NSCLC) xenografts were examined (13 adenocarcinoma, 18 squamous cell carcinoma and 8 large cell carcinoma). Significant expression of the MUC6 gene was observed in 7 out of 39 (17.9%) NSCLC xenografts. The expressions of the MUC6 genes were noted in 6 out of 13 (46.2%) adenocarcinoma xenografts, but only in 1 of 18 (0.06%) squamous cell carcinoma xenografts. The adenocarcinoma xenografts significantly showed higher expression of the MUC6 gene than squamous cell carcinoma xenografts (t-test, p=0.0343). Four adenocarcinoma-xenografts co-expressed both the MUC2 and MUC6 genes, and the residual 2 adenocarcinoma-xenografts expressed only the MUC6 gene. One MUC6 overexpressing squamous cell carcinoma focally contained an adenocarcinoma component. The expression patterns of the gastrointestinal mucins were analogous to gastric cancer. The cellular morphology of these carcinoma xenografts was of the gastric cancer type. The proteins of the MUC2 and MUC6 were immunohistochemically confirmed in the xenografts. The expression of the MUC6 gene was significantly correlated with the expressions of the CDX1 and CDX2 genes in the xenografts (Fisher's test, p<0.0001 and p=0.0005, respectively), while there was no significant association between the expression of the MUC2 and CDX genes. These results suggest that the expression of CDX molecules in the pulmonary carcinogenesis pathway relates to gastric cancerous features of aberrant MUC6 expression.
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PMID:Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts. 1575 82

Gastric atrophy and intestinal metaplasia are generally considered to be precancerous lesions of the stomach. Chronic Helicobacter pylori infection is one the most important factors in the development of these pre-malignant gastric lesions. In addition to bacterial factors, polymorphisms in the cytokine genes of the host that modulate inflammatory responses are found to have a synergistic effect in the development of gastric cancer as well as pre-neoplastic lesions. Recently, inappropriate activation of the intestine-specific transcription factor like the homeobox gene complex CDX1 and CDX2 are found to be an important contributing factor in the induction of intestinal metaplasia in the stomach. Aberrant expression of cyclooxygenase-2 and epigenetic changes are also frequently detected in pre-neoplastic gastric lesions. One of the most important questions relating to these pre-neoplastic gastric lesions is that whether H. pylori eradication could reverse these changes. However, most controlled studies showed no or just modest improvement in intestinal metaplasia after H. pylori eradication. Further studies should evaluate the role of other chemopreventive agents, particularly cyclooxygenase-2 inhibitor, on regression of pre-neoplastic lesions.
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PMID:Pathogenesis of pre-neoplastic lesions of the stomach: targets for prevention. 1581 52

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-/- cells are essentially identical to their parental cells, with the exception of CDX2 ablation. We found no significant differences in the proliferation of CDX2-/- cells compared to CDX2+/+ 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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PMID:CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45. 1633 Dec 67

Helicobacter pylori plays a causative role in the development of chronic atrophic gastritis, intestinal metaplasia (IM), and stomach cancer. Although IM has long attracted attention as a putative preneoplastic lesion for stomach cancers, its clinicopathologic significance has yet to be clarified in detail. Using gastric and intestinal epithelial cell markers, IM was here divided into two major types: a gastric-and-intestinal (GI) mixed type and a solely intestinal (I) type. In the former, gastric and intestinal phenotypic markers appeared not only at the glandular but also at the cellular level. Furthermore, neuroendocrine cells also showed intestinalization along with their exocrine counterparts. In animal models, GI-type IM was found to appear first, followed by the solely I type. Summarizing these data, it was suggested that IM might be caused by the gradual intestinalization of stem cells from the GI to the I type. The molecular mechanisms of IM include the ectopic expression of CDX1, CDX2, OCT-1, and members of the Erk pathway. Suppression of the expression of gastric transcription factors such as SOX2, genes that are involved in the Sonic hedgehog pathway, and RUNX3, a tumor suppressor gene, could be additional relevant alterations. The expression of PDX1 may also be associated with pseudopyloric gland metaplasia and IM. Detailed analysis of gene regulation may shed light on the molecular bases of gastric lesions, leading to strategies for chemoprevention.
Gastric Cancer 2006
PMID:Gastric-and-intestinal mixed-type intestinal metaplasia: aberrant expression of transcription factors and stem cell intestinalization. 1695 33

Loss of Sonic Hedgehog (Shh) and aberrant CDX2 expression are early changes correlating with the presence of intestinal metaplasia that occur in the gastric mucosa prior to neoplastic transformation. The aim of this study was to compare the improvement in corpus gastritis with Shh and CDX2 expression after H. pylori eradication between subjects at high risk for gastric cancer and controls. The usefulness of serum pepsinogen levels as a predictor of resolved corpus gastritis was also examined. Seventy patients with endoscopic resection for early gastric cancer and 30 controls were studied. Expression of Shh and CDX2 were evaluated by immunostaining. Serum levels of pepsinogen I before eradication in the patients scored as having improvement of corpus atrophy were significantly higher than in the patients without improvement (<0.01). Residual inflammation at the corpus lesser curve was more frequently detected in the cancer group than in the controls (OR 4.6 95% C.I. 1.6-13.5) and in the mucosa with incomplete intestinal metaplasia rather than in those without incomplete intestinal metaplasia (OR 7.6 95% C.I. 2.4-24.3). Atrophy, expression of Shh and CDX2 at the corpus lesser curve significantly improved in mucosa without incomplete intestinal metaplasia (p < 0.01), but not in mucosa with incomplete intestinal metaplasia. In conclusion, H. pylori eradication prior to development of incomplete intestinal metaplasia improves corpus gastritis and may prevent gastric cancer. Pepsinogen I may be a useful marker in patients with a residual higher risk of gastric cancer after H. pylori eradication.
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PMID:Re-expression of sonic hedgehog and reduction of CDX2 after Helicobacter pylori eradication prior to incomplete intestinal metaplasia. 1752 Jun 81


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