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)

Proteins of the cadherin family regulate cellular adhesion and motility and are believed to act as tumour suppressors. Previous studies have identified frequent mutation and allelic inactivation of the E-cadherin (cadherin-1) locus in diffuse gastric cancer. At least two other cadherin genes, P-cadherin (cadherin-3) and OB-cadherin (cadherin-11), have been mapped close to the E-cadherin gene on chromosome 16q22. As this region of the genome is frequently deleted in malignancy, multiple cadherin loci may be affected by losses of chromosome 16q22. The expression of mRNA transcripts from polymorphic alleles of the E-cadherin and cadherin-11 genes was examined in 30 cases of colonic, gastric, and renal carcinoma. In gastric cancer, loss of expression of one allele was restricted to the E-cadherin locus, whilst in renal carcinoma neither locus was affected. In colonic cancers, loss of expression of one E-cadherin allele was detected in 5 of 22 cases, whilst loss of a cadherin-11 allele was seen in 5 of 23 cases. This functional loss of cadherin gene expression may be due to gene deletion, inactivation or recombination. As no evidence of cadherin gene mutation was observed in the remaining transcripts, we can conclude that these two genes are only indirectly involved in the pathogenesis of colorectal cancer.
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PMID:Functional loss of E-cadherin and cadherin-11 alleles on chromosome 16q22 in colonic cancer. 1039 17

Although the advancement of molecular oncology in gastric cancer lags behind that of colorectal cancer, the rapid developments witnessed in recent years have improved our understanding of the carcinogenesis, aetiology, progression and metastasis of gastric cancer. The different molecular genetic alterations in intestinal and diffuse types of gastric cancer have further supported the concept that these two pathological types are different disease entities. The association of telomerase and cadherin changes with Helicobacter pylori infection reinforces its aetiological role. The mutated cadherin gene identified in familial gastric cancer has shone light onto the pathogenesis. Adhesion molecules have already been applied to daily clinical practice as prognostic markers. Future molecular studies will contribute to the screening, classification, disease monitoring and therapeutics of gastric cancer.
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PMID:Molecular biology of gastric carcinoma: from laboratory to bedside. 1063 50

Our previous comparative genomic hybridization (CGH) study revealed a novel amplified region at 15q26 in two cell lines established from diffuse types of gastric cancer (GC). In this amplified region, FES and IGF1R, known targets on 15q26, were located telomeric to the amplicon in the two cell lines, HSC39 and 40A, suggesting that another tumor-associated gene exists in this region. While screening expressed sequence tags (ESTs) for novel genes in this region, we identified the IQGAP1 amplification. IQGAP1 has been reported to encode a ras GAP-related protein, and its interaction with cadherin and/or beta-catenin induces a dissociation of beta-catenin from the cadherin-catenin complex, one of the mechanisms for cell-cell adhesion. Northern and Western blot analyses revealed that amplification of this gene was accompanied by corresponding increases in mRNA and protein expression. Moreover, immunocytochemical staining showed that overexpressed IQGAP1 accumulated at the membrane, suggesting its colocalization with beta-catenin. Taken together, these findings suggest that IQGAP1 may be one of the target genes in the 15q26 amplicon correlated with a malignant phenotype of gastric cancer cells, such as diffuse and invasive characteristics, through the disruption of E-cadherin-mediated cell-cell adhesion.
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PMID:IQGAP1, a negative regulator of cell-cell adhesion, is upregulated by gene amplification at 15q26 in gastric cancer cell lines HSC39 and 40A. 1128 14

Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and beta-catenin by immunohistochemistry and for methylation of the CDH1 promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDH1 promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDH1 promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of beta-catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer.
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PMID:Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis. 1166 47

Nectin is an immunoglobulin-like adhesion molecule that comprises a family consisting of four members, nectin-1, -2, -3, and -4. Nectin is associated with the actin cytoskeleton through afadin, a nectin- and actin filament-binding protein. The nectin-afadin and cadherin-catenin systems are associated with each other and cooperatively form cell-cell adherens junctions in intact epithelial cells. HSC-39 cells, a human signet ring cell gastric cancer cell line, express E-cadherin but do not form cell-cell adhesion. The beta-catenin gene has been shown to be truncated at the N-terminal region including the alpha-catenin-binding domain in HSC-39 cells, but overexpression of normal beta-catenin failed to form cell-cell adhesion. HSC-39 cells expressed nectin-1, -2, and afadin, but not nectin-3. Overexpression of nectin-3 or -2 formed cell-cell adhesion and accumulation of E-cadherin, but not actin filaments, at the cell-cell adhesion sites. Overexpression of a truncated form of nectin-2 incapable of interacting with afadin failed to form cell-cell adhesion. However, the nectin-formed cell-cell adhesion was not so strong as that observed in epithelial cells, such as CaCo-2 cells. Co-expression of nectin-2 and normal beta-catenin did not form strong cell-cell adhesion. These results suggest that an unidentified mechanism, by which nectin and E-cadherin form the actin cytoskeleton-associated adherens junctions to form strong cell-cell adhesion, is impaired in HSC-39 cells.
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PMID:Restoration of E-cadherin-based cell-cell adhesion by overexpression of nectin in HSC-39 cells, a human signet ring cell gastric cancer cell line. 1203 67

The cadherin-catenin complex has been recognized as an important factor associated with tumor metastasis. However, the clinical significance of the expression of adhesion molecules in lymph nodes with metastasis remains unclear. The aim of this study was to investigate the clinical significance of the re-expression of the cadherin-catenin complex in metastatic lymph nodes in patients with advanced gastric cancer. Immunohistochemical expression of E-cadherin, alpha- and beta-catenin were analyzed in 96 primary gastric cancers with serosal invasion and in 79 lymph nodes with metastasis. The expression levels of these adhesion molecules in primary tumors and lymph nodes with metastasis were compared. Ninety-four out of 96 primary tumors (98%) showed reduced expression of adhesion molecules. Out of 79 cases with lymph node metastasis, increased expression of one or more adhesion molecules in metastatic foci as compared with primary tumors was detected in 52 cases (66%). Re-expression of adhesion molecules in metastatic lymph nodes was detected in a more advanced stage. The overall 5-year survival rate of the 52 patients who had lymph nodes with metastasis with re-expression of adhesion molecules (8%) was significantly poorer than that of the 27 who had lymph nodes with metastasis without re-expression of adhesion molecules (33%, P = 0.0012). The re-expression of the cadherin-catenin complex in lymph nodes with metastasis may play an important role in the growth of cancer cells in metastatic foci. A comparison of the expression patterns of adhesion molecules between the primary tumor and metastatic lymph nodes may provide new prognostic information for patients with advanced gastric cancer.
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PMID:Re-expression of the cadherin-catenin complex in lymph nodes with metastasis in advanced gastric cancer: the relationship with patient survival. 1207 32

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

We report the association of CDH1/E-cadherin mutations with cleft lip, with or without cleft palate (CLP), in two families with hereditary diffuse gastric cancer (HDGC). In each family, the CDH1 mutation was a splicing mutation generating aberrant transcripts with an in-frame deletion, removing the extracellular cadherin repeat domains involved in cell-cell adhesion. Such transcripts might encode mutant proteins with trans-dominant negative effects. We found that CDH1 is highly expressed at 4 and 5 weeks in the frontonasal prominence, and at 6 weeks in the lateral and medial nasal prominences of human embryos, and is therefore expressed during the critical stages of lip and palate development. These findings suggest that alteration of the E-cadherin pathway can contribute to human clefting.
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PMID:Cleft lip/palate and CDH1/E-cadherin mutations in families with hereditary diffuse gastric cancer. 1583 93

Cyclooxygenase-2 (COX-2) plays a crucial role in the development and invasion of gastric cancer. COX-2 inhibitors have been shown to be chemopreventive against gastrointestinal cancers. In vitro studies have suggested that the mechanisms may be related to induction of apoptosis and inhibition of angiogenesis. COX-2 may also have impact on E-cadherin. In our study we investigate the effect of Celecoxib on expression of E-cadherin and serum soluble E-cadherin, as well as on apoptosis and angiogenesis in patients with gastric cancer. Fifty nine gastric cancer patients were randomly divided into two groups: Surgery group (n = 22), in which patients underwent surgical resection after diagnosis, and Celecoxib + Surgery group (n = 37), in which patients received oral Celecoxib 200 mg twice daily for 7 days before curative resection. Twenty healthy subjects (Healthy controls) were recruited as normal controls. After curative resection, COX-2, E-cadherin, VEGF, and MVD were detected by immunohistochemistry. Serum soluble E-cadherin was quantitatively measured using a commercially available enzyme-linked immunosorbent assay kit. Apoptosis was determined by TUNEL assay. Significantly decreased expression of COX-2, increased E-cadherin and apoptosis, decreased VEGF and MVD were observed in gastric cancer tissues from patients receiving Celecoxib compared to Surgery group. Compared to Healthy controls, the serum soluble E cadherin levels were higher in gastric cancer patients which were decreased by Celecoxib. This in vivo study demonstrated that Celecoxib induces apoptosis and inhibit angiogenesis of gastric cancer. Its impact on E-cadherin may suggest that this agent may suppress the invasion of advanced gastric cancer.
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PMID:Effect of celecoxib on E-cadherin, VEGF, Microvessel density and apoptosis in gastric cancer. 1742 34

The aims of this study were to examine Li-cadherin expression in 74 gastric carcinoma tissues, 10 cases with normal gastric tissues, and 21 cases with intestinal metaplasia and to investigate the role of Li-cadherin in cell differentiation, cancer invasion, and metastasis. Expression of Li-cadherin was analyzed by immunohistochemistry and semiquantitative polymerase chain reaction and correlated with clinicopathological parameters. Immunohistochemistry showed that Li-cadherin was mainly present on the cell membrane and there was no staining for liver-intestine cadherin in normal tissues. The reduction of Li-cadherin mRNA expression was inversely correlated with the grade of differentiation (P < 0.05). Significant differences in the expression of liver-intestine cadherin were found in lymphatic metastasis of the tumors (P < 0.05), but the expression of liver-intestine cadherin was not associated with gender (P=0.748), serosal invasion (P=0.136), TNM stage (P=0.172), Helicobacter pylori infection (P=0.572), liver metastasis (P=0.374), or peritoneal metastasis (P=0.621). Multivariate analysis revealed that the expression of Li-cadherin is an important predictor of lymph node metastasis. We conclude that there is a significant correlation between Li-cadherin expression and the differentiation of gastric carcinoma, and Li-cadherin can be a good marker to detect gastric cancer at early stages. Increased Li-cadherin expression may contribute to gastric cancer invasion to lymph nodes.
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PMID:Altered expression of a Li-cadherin in gastric cancer and intestinal metaplasia. 1722 75


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