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)

WNT signal is transduced to the beta-catenin - TCF pathway, the JNK pathway, or the Ca2+-releasing pathway through seven-transmembrane-type WNT receptors encoded by Frizzled genes (FZD1-FZD10). We have previously cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, and WNT14B/WNT15 by using bioinformatics, cDNA-library screening, and cDNA-PCR. Here, we investigated expression of human WNT5A mRNA in various normal tissues, 66 primary tumors derived from various tissues, and 15 human cancer cell lines. WNT5A mRNA was relatively highly expressed in salivary gland, bladder, uterus, placenta, and fetal kidney. Up-regulation of WNT5A mRNA was detected in 5 out of 8 cases of primary gastric cancer, 5 out of 18 cases of primary colorectal tumors, and in 2 out of 7 cases of primary uterus tumors by using matched tumor/normal expression array analysis. Up-regulation of WNT5A mRNA was also detected in 7 out of 10 other cases of primary gastric cancer by using cDNA-PCR. Although low-level expression of WNT5A mRNA was detected in gastric cancer cell line MKN45, WNT5A mRNA was almost undetectable in gastric cancer cell lines OKAJIMA, TMK1, MKN7, MKN28, MKN74, and KATO-III. Compared with frequent up-regulation of WNT5A mRNA in primary gastric cancer, expression levels of WNT5A mRNA in 7 gastric cancer cell lines were significantly lower than that in normal stomach. Frequent up-regulation of WNT5A mRNA in human primary gastric cancer might be due to cancer-stromal interaction.
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PMID:Frequent up-regulation of WNT5A mRNA in primary gastric cancer. 1195 59

BACKGROUND: Beta-catenin plays two distinct roles, in intercellular adhesion by E-cadherin, and in transcriptional activation via TCF/LEF. Theoretically, the former role is tumor-suppressive, while the latter is oncogenic. We investigated the involvement of beta-catenin in the histogenesis and clinical outcome of gastric cancers.METHODS: The expression pattern of beta-catenin was evaluated in stomach and lymph nodes from 82 patients with gastric cancer by immunohistochemistry and Western blot. Its association with E-cadherin expression and clinicopathological factors, including histological type and postoperative survival, was examined.RESULTS: Beta-catenin expression was classified into two patterns, normal (23.2%; 19 patients) and disordered (76.8%; 63 patients), the latter being subclassified as overexpressed (7.3%; 6 patients) and reduced (69.5%; 57 patients). A disordered beta-catenin expression pattern was significantly correlated with diffuse type adenocarcinoma and deep tumor infiltration ( P = 0.0154), but was not associated with lymph node metastasis ( P = 0.7877). E-cadherin was always expressed at the cell membrane, and disordered beta-catenin expression was significantly associated with reduced E-cadherin expression ( P < 0.0001). On univariate analysis, the beta-catenin pattern, as well as depth of invasion and lymph node metastasis, was associated with postoperative prognosis; however, only lymph node metastasis was an independent prognostic factor on multivariate analysis. Interestingly, different disordered patterns of beta-catenin expression, both overexpressed and reduced, were associated with E-cadherin reduction and poorer postoperative survival.CONCLUSION: Although disordered patterns of beta-catenin expression varied in gastric cancers, they were consistently associated with cancer progression.
Gastric Cancer 2000 Dec
PMID:Clinical significance of disordered beta-catenin expression pattern in human gastric cancers. 1198 36

Xenopus Strabismus (Stbm) is a negative regulator of the WNT - beta-catenin signaling pathway. Strabismus 1 (STB1/VangL2) and Strabismus 2 (STB2/Vangl1) are human homologues of Xenopus Stbm and Drosophila Stbm/ Van Gogh (Vang) STB1 and STB2 are four-transmembrane-type proteins with Dishevelled-binding motif. STB2 and CASQ2 genes are located on human chromosome 1p13.3-p11 with an interval less than 5 kb. Here, STB1 gene and CASQ1 gene were found to be located on human chromosome 1q21-q23 with an interval of about 210 kb including Nicastrin, COPA, PXF, H326 and PEA15 genes. Exon-intron structure was well conserved between STB1 and STB2 genes. STB1-CASQ1 gene cluster and STB2-CASQ2 gene cluster might be generated due to duplication of ancestral gene cluster, and several genes might be inserted into the STB1-CASQ1 intergenic region during or after gene-cluster duplication. STB1 mRNA was relatively highly expressed in prostate, trachea, thymus, lymph node, placenta, fetal kidney, fetal brain, and fetal lung. In adult brain, STB1 mRNA was more highly expressed in cerebellum, corpus callosum, amygdala, and medulla oblongata. STB1 mRNA was moderately expressed in K-562 (chronic myelogenous leukemia), G-361 (melanoma), and MKN7 (gastric cancer). On the other hand, STB1 mRNA was almost undetectable in several human cancer cell lines, and was down-regulated in 4 out of 14 cases of primary kidney tumors, and in 2 out of 3 cases of primary lung cancer. Loss-of-function mutation of STB1 gene might lead to carcinogenesis through activation of the WNT - beta-catenin signaling pathway.
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PMID:Structure and expression of Strabismus 1 gene on human chromosome 1q21-q23. 1201 99

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

Strabismus 1 (STB1/VANGL2) and Strabismus 2 (STB2/VANGL1), which have been cloned and characterized using bioinformatics and cDNA-PCR, are human homologues of Drosophila tissue polarity gene strabismus (stbm)/Van Gogh (Vang). STB1 and STB2 are tetra-membrane-spanning proteins with 73.1% total-amino-acid identity. Serine-rich domain and Strabismus-homology (STH1 and STH2) domains are conserved among human STB1, STB2, Xenopus Stbm, and Drosophila Stbm. STH2 domain with the C-terminal Ser/Thr-X-Val motif is implicated in binding with Dishevelled (DVL) proteins. STB1 gene is clustered with CASQ1 gene on human chromosome 1q21-q23, while STB2 gene is clustered with CASQ2 gene on human chromosome 1p13. STB1 and STB2 genes are located around cancer susceptibility loci or recombination hot spots in the human genome. STB1 is moderately expressed in K-562 (leukemia), G-361 (melanoma), and MKN7 (gastric cancer) cells. STB2 is highly expressed in MKN28, MKN74 (gastric cancer), BxPC-3, PSN-1, and Hs766T (pancreatic cancer) cells. On the other hand, STB1 and STB2 are significantly down-regulated in several cancer cell lines and primary tumors. Xenopus homologue of human STB1 and STB2 regulates negatively the WNT - beta-catenin signaling pathway. Loss-of-function mutations of genes encoding negative regulators of WNT - beta-catenin signaling pathway lead to carcinogenesis. Based on functional aspects and human chromosomal loci, STB1 gene and STB2 gene are predicted to be potent tumor suppressor gene candidates. STB1 and STB2 might be suitable targets for tissue engineering in the field of re-generative medicine and for chemoprevention and treatment in the field of clinical oncology.
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PMID:Strabismus (STB)/Vang-like (VANGL) gene family (Review). 1206 Aug 45

Studies of Wnt activation in gastric cancer have yielded conflicting results. The goals of this study were to determine the frequency of Wnt pathway activation and beta-catenin mutation in these tumors. Three hundred eleven gastric cancers were examined for beta-catenin expression by immunostaining and dissected using laser capture microscopy to obtain DNA from those tumors with nuclear beta-catenin. Exon 3 of beta-catenin was amplified using PCR and sequenced. Ninety gastric cancers (29%) displayed nuclear beta-catenin. DNAs from 73 tumors were amplified and sequenced; 19 (26%) contained mutations in exon 3 of beta-catenin, whereas no mutations were detected in 19 tumors negative for beta-catenin nuclear staining (P < 0.05). Most mutations were adjacent to or abolished known regulatory phosphorylation sites. Mutations in exon 3 of beta-catenin are common in gastric cancer that display nuclear beta-catenin. These results suggest that Wnt pathway activation contributes to carcinogenesis in a subset of gastric adenocarcinomas.
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PMID:beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. 1206 95

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

Gastric cancer is common among the world, but genetic mechanisms of gastric carcinogenesis are not well understood. Gastric polypoid adenomas and flat dysplasias are regarded as precursor lesions. However, a detailed molecular study of these lesions has not been done to determine their role as precancerous lesions. We investigated mutations of the APC, beta-catenin, and K-ras genes, and microsatellite instability (MSI) status in 35 adenomas and 47 flat dysplasias without adenocarcinoma, 35 adenomas/dysplasias associated with adenocarcinomas, and 39 adenocarcinomas (20 diffuse type and 19 intestinal type). Somatic APC gene mutations were identified in 76% (59 of 78) of adenomas or flat dysplasias without associated adenocarcinoma, but in only 3% (1 of 30) of adenomas/dysplasias associated with adenocarcinoma, and in only 4% (3 of 69) of adenocarcinomas (P < 0.000001). No mutations of beta-catenin were found in adenocarcinomas, or adenomas/dysplasia without APC mutation. K-ras mutations were detected in 5% (4 of 82) of gastric adenomas/dysplasia without carcinoma, 3% (1 of 39) of adenocarcinomas without associated adenoma/dysplasia, and not in 32 adenocarcinomas with associated adenoma/dysplasia. High level of MSI (MSI-H) was more frequent in gastric adenoma/dysplasia associated with carcinoma (17%, 6 of 35) than in adenomas/dysplasia without carcinoma (3%, 2 of 75; P = 0.01). MSI-H was also more frequent in intestinal type adenocarcinoma (20%, 11 of 54) than in diffuse type (0%, 0 of 20; P = 0.03). APC gene mutations were present in six of nine (67%) of gastric adenomas/dysplasias with low level of MSI, but in none of the eight adenomas/dysplasia with MSI-H phenotype (P = 0.009). Our results indicate that somatic mutation of the APC gene plays an important role in the pathogenesis of gastric adenoma and dysplasia but has a limited role in neoplastic progression to adenocarcinoma. Gastric adenomas or dysplasias without APC mutations but with or without MSI may have a different biological behavior, and are precursors of intestinal-type of gastric adenocarcinomas.
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PMID:Inverse relationship between APC gene mutation in gastric adenomas and development of adenocarcinoma. 1216 85

SOX proteins are a family of transcription factors with high-mobility-group DNA-binding domain (HMG box) homologous to SRY, which play key roles in embryogenesis. Xenopus Sox17alpha, Sox17beta, Sox3 and mouse Sox7 are reported to be negative regulators of the WNT-beta-catenin-TCF signaling pathway. SOX7, SOX17, and SOX18 constitute a subfamily among the SOX gene family. Here, expression of SOX18 mRNA was investigated using Northern blot analysis, RNA dot blot analysis, and cDNA-PCR. SOX18 mRNA was significantly highly expressed in ventricles and inter-ventricular septum of adult heart among various normal human tissues. SOX18 mRNA was relatively highly expressed in stomach and jejunum in the gastrointestinal tract. SOX18 mRNA was relatively highly expressed in TMK1 and MKN45 among 7 gastric cancer cell lines. SOX18 mRNA was expressed in all out of 7 pancreatic cancer cell lines, and was relatively highly expressed in PANC-1, Hs700T, Hs766T and MIA PaCa-2. Expression level of SOX18 mRNA in MCF-7 cells (breast cancer) was not affected by beta-estradiol. SOX18 mRNA was expressed in all out of 5 embryonal tumor cell lines, and was relatively highly expressed in NT2 with the potential to differentiate into neuronal cells. Expression level of SOX18 mRNA in NT2 cells was down-regulated by all-trans retinoic acid. This is the first report on comprehensive expression analyses of SOX18 mRNA in normal human tissues and tumors.
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PMID:Expression of human SOX18 in normal tissues and tumors. 1216 11

WNT signaling pathway plays key roles in carcinogenesis and embryogenesis, and WNT signaling molecules are potent targets for diagnosis, prevention and treatment of cancer as well as for regenerative medicine or tissue engineering. We have so far cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14 and WNT14B/WNT15 using bioinformatics and cDNA-PCR. We have also reported frequent up-regulation of WNT2 and WNT5A in primary gastric cancer, which is probably due to cancer-stromal interaction. Here, expression and regulation of WNT5A and WNT5B in human cancer were investigated. WNT5A was relatively highly expressed in TE6 and TE10 among 12 esophageal cancer cell lines, and WNT5B was expressed in the majority of esophageal cancer cell lines. Among 7 pancreatic cancer cell lines, WNT5A was up-regulated in Hs700T, and WNT5B in PANC-1. WNT5A, but not WNT5B, was up-regulated by TNFalpha in MKN45 cells derived from gastric cancer. WNT5B, but not WNT5A, was up-regulated by beta-estradiol in MCF-7 cells derived from breast cancer. WNT5A and WNT5B were expressed together in 5 embryonal tumor cell lines, and were slightly down-regulated by all-trans retinoic acid in NT2 cells. Up-regulation of WNT5A and WNT5B in several types of human cancer expressing FZD5 might lead to more malignant phenotype through activation of the beta-catenin - TCF pathway.
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PMID:Expression and regulation of WNT5A and WNT5B in human cancer: up-regulation of WNT5A by TNFalpha in MKN45 cells and up-regulation of WNT5B by beta-estradiol in MCF-7 cells. 1216 12


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