Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secreted glycoprotein WNTs play important roles in carcinogenesis and development. We have previously reported molecular cloning of WNT-2B/WNT-13. Here, we have isolated a novel WNT-2B isoform (WNT-2B2), in addition to the original WNT-2B isoform (WNT-2B1). WNT-2B1 and WNT-2B2 are completely different in the 5'-UTR and in the N-terminal part of the coding region. The N-terminal hydrophobic domain is contained in WNT-2B1, but not in WNT-2B2. WNT-2B1 and WNT-2B2 share the WNT-core domain, and show 87.0% amino-acid identity. We have determined the structure of the WNT-2B gene. The WNT-2B1 mRNA consists of exons 1, 2, and 4-7, while the WNT-2B2 mRNA consists of exons 3-7. WNT-2B2 was expressed in fetal brain, fetal lung, fetal kidney, caudate nucleus, testis, glioblastoma cell lines A172, SW1783, gastric cancer cell lines MKN28, MKN74, and cervical cancer cell line HeLa S3. WNT-2B1 expression level was relatively higher in fetal brain and fetal lung than in other tissues or cell lines expressing WNT-2B2. These results indicate that the WNT-2B1 and WNT-2B2 mRNAs are transcribed due to alternative splicing with distinct expression profile. This is the first report on the WNT isoforms derived from the same gene due to alternative splicing.
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PMID:Alternative splicing of the WNT-2B/WNT-13 gene. 1094 66

WNT2 is one of proto-oncogenes with the potential to activate the WNT - beta-catenin - TCF signaling pathway, which is most homologous to WNT2B among members of the human WNT gene family. Here, expression of WNT2 mRNA was comprehensively investigated. WNT2 mRNAs were highly expressed in fetal lung, and weakly expressed in placenta. Among 2.0-, 2.9-, 4.1-, and 6.0-kb WNT2 mRNAs, the 2.0-kb WNT2 mRNA was the major transcript in fetal lung. In 3 cases of prostate cancer and 1 case each of lung cancer and cervical cancer, WNT2 was over-expressed in non-cancerous portion as well as in primary tumor. WNT2 was up-regulated in 14 out of 18 cases of primary colorectal cancer, 4 out of 7 cases of uterus tumor, 2 out of 9 cases of breast cancer, and in 2 out of 14 cases of kidney tumor. Up-regulation of WNT2 was also detected in 4 out of 8 cases of primary gastric cancer by using expression array filter hybridization, and in 10 out of another 10 cases of primary gastric cancer by using cDNA-PCR. Frequent up-regulation of WNT2 in primary gastric cancer and colorectal cancer might play a key role in carcinogenesis through activation of the WNT - beta-catenin - TCF signaling pathway.
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PMID:Frequent up-regulation of WNT2 in primary gastric cancer and colorectal cancer. 1160 1

Genetic alterations of WNT signaling molecules lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway. We have previously cloned and characterized WNT2B/WNT13 gene on human chromosome 1p13, which is homologous to proto-oncogene WNT2 on human chromosome 7q31. WNT2B1 and WNT2B2 mRNAs, generated from the WNT2B gene due to alternative splicing of the alternative promoter type, encode almost identical polypeptides with divergence in the N-terminal region. WNT2B2 mRNA rather than WNT2B1 mRNA is preferentially expressed in NT2 cells with the potential of neuronal differentiation. Here, we describe our investigations of expression of WNT2B mRNAs in various types of human primary cancer. Matched tumor/normal expression array analysis revealed that WNT2B mRNAs were significantly up-regulated in 2 of 8 cases of primary gastric cancer. WNT2B2 mRNA rather than WNT2B1 mRNA was found to be preferentially up-regulated in a case of primary gastric cancer (signet ring cell carcinoma). Function of WNT2B1 mRNA and that of WNT2B2 mRNA were investigated by using Xenopus axis duplication assay. Injection of synthetic WNT2B1 mRNA into the ventral marginal zone of fertilized Xenopus eggs at the 4-cell stage did not induce axis duplication. In contrast, ventral injection of synthetic WNT2B2 mRNA induced axis duplication in 90% of embryos (complete axis duplication, 24%). These results strongly suggest that WNT2B2 up-regulation in some cases of gastric cancer might lead to carcinogenesis through activation of the beta-catenin-TCF signaling pathway.
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PMID:WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT- beta-catenin-TCF signaling pathway. 1174 4

WNTs are a family of secreted-type glycoproteins implicated in embryogenesis and carcinogenesis. We have previously cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, and WNT14B/WNT15. WNT14B gene is clustered with WNT3 gene in human chromosome 17q21, and mRNA expression of WNT14B is significantly up-regulated by retinoic acid during the early phase of neuronal differentiation in human NT2 cells. Here, we identified mouse Wnt14b gene fragments in mouse genome draft sequence AL596108.5 by using bioinformatics, and isolated mouse Wnt14b cDNAs by using cDNA-PCR. Mouse Wnt14b was found to encode a 359-amino-acid WNT family protein with the N-terminal signal peptide, an N-linked glycosylation site, and 24 conserved cysteine residues. Mouse Wnt14b showed 92.5% total-amino-acid identity with human WNT14B, and 64.2% total-amino-acid identity with human WNT14. Mouse Wnt14b gene, consisting of 4 exons, was clustered with mouse Wnt3 gene in mouse chromosome 11. Mouse Wnt14b mRNA was relatively highly expressed in 17-day embryo, and also expressed in adult brain, kidney, liver, 7-day embryo, and 11-day embryo. This is the first report on molecular cloning and characterization of mouse Wnt14b.
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PMID:Molecular cloning and characterization of mouse Wnt14b, clustered with mouse Wnt3 in mouse chromosome 11. 1178 23

WNT - beta-catenin - TCF signaling pathway is activated by Xenopus wnt-8 (Xwnt-8) during Xenopus early development, and dysregulated activation of beta-catenin - TCF signaling pathway in mammalian cells leads to carcinogenesis. We have previously cloned and characterized human WNT8A, one of human orthologues of Xwnt-8. Here, we cloned and characterized human WNT8B by using bioinformatics, cDNA-PCR, and RACE. WNT8B gene of about 23-kb in size consisted of six exons, and encoded a 351-amino-acid polypeptide with the N-terminal signal peptide and two N-linked glycosylation sites. C-terminal region of WNT8B, WNT8A, WNT2, and WNT2B were longer than that of other human WNTs. Thirty-five nucleotide changes between WNT8B isolated by us and WNT8B isolated by another group resulted in Gly230Ala and Arg284Leu amino-acid substitutions. Gly230 and Arg284 of WNT8B were conserved in WNT8A. Gly230-Arg284 WNT8B allele was also identified in human genome draft sequences AL133352.10, AL359759.18, and human EST BF732616. These results indicate that the Gly230-Arg284 WNT8B cDNA isolated in this study is derived from the more common WNT8B allele. WNT8B mRNAs of 4.4- and 3.5-kb in size were weakly detected in a colorectal cancer cell line SW480, but were undetectable in any normal human tissues by using Northern blot analyses. WNT8B was significantly up-regulated in gastric cancer cell lines KATO-III (signet-ring cell carcinoma) and MKN45 (poorly differentiated adenocarcinoma), and also in 5 out of 10 cases of primary gastric cancer. WNT8B might play key roles in gastric cancer through activation of the beta-catenin - TCF signaling pathway.
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PMID:Up-regulation of WNT8B mRNA in human gastric cancer. 1178 99

We have previously cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT10A, WNT10B, WNT11, WNT14, and WNT14B/WNT15 by using bioinformatics, cDNA-library screening, cDNA-PCR, and RACE. WNT3 and WNT3A genes are two human paralogues of mouse proto-oncogene Wnt3, which induces carcinogenesis through activation of the beta-catenin - TCF signaling pathway. Here, regulation of WNT3 and WNT3A mRNAs in human cancer cell lines was investigated. WNT3 and WNT3A mRNAs were co-expressed in an embryonal carcinoma cell line NT2, which is reported to differentiate into postmitotic CNS neurons by treatment with retinoic acid for two weeks. Expression level of WNT3 mRNA in NT2 cells was not changed during 72 h after retinoic acid treatment, while expression of WNT3A mRNA was down-regulated in NT2 cells by retinoic acid. WNT3 and WNT3A mRNAs were also co-expressed in a breast cancer cell line MCF-7, and were down-regulated together by beta-estradiol in MCF-7 cells. Expression of WNT3 mRNA in a gastric cancer cell line MKN45 was not changed after treatment with tumor necrosis factor alpha (TNFalpha) or interferon gamma (IFNgamma), and that of WNT3A mRNA was undetectable before and after treatment with TNFalpha or IFNgamma. WNT3A, down-regulated by retinoic acid in NT2 cells, might play key roles in the maintenance of NT2 cells in the undifferentiated proliferation stage through activation of the beta-catenin - TCF signaling pathway.
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PMID:Regulation of WNT3 and WNT3A mRNAs in human cancer cell lines NT2, MCF-7, and MKN45. 1178 4

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

WNT family of secreted-type glycoproteins play key roles in carcinogenesis and embryogenesis. We have 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, and also reported frequent up-regulation of WNT2 in primary gastric cancer. Here, expression and regulation of WNT1 in human cancer were investigated using cDNA-PCR. WNT1 mRNA was relatively highly expressed in OKAJIMA cells (gastric cancer) and BxPC-3 cells (pancreatic cancer). Expression of WNT1 mRNA was up-regulated in 5 out of 10 cases of primary gastric cancer. Effects of beta-estradiol on expression of human WNT1 in MCF-7 cells (breast cancer) was next investigated, because mouse Wnt-1 induces mammary carcinogenesis even in estrogen receptor alpha (ERalpha) knockout mice. Expression of WNT1 mRNA was significantly up-regulated by beta-estradiol in MCF-7 cells. WNT1 was found to be one of estrogen target genes in human MCF-7 cells, which in part explains Wnt1-induced mammary carcinogenesis in ERalpha knockout mice.
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PMID:Expression and regulation of WNT1 in human cancer: up-regulation of WNT1 by beta-estradiol in MCF-7 cells. 1246 6

WNT2 gene on human chromosome 7q31 is a paralog of the WNT2B gene on human chromosome 1p13. Rat Wnt2 gene was identified within rat genome draft sequence AC095247.4. Human WNT2 showed 96.4% total-amino-acid identity with rat Wnt2, 96.1% with mouse Wnt2, 68.6% with zebrafish wnt2, and 67.8% with fugu wnt2. WNT2 is an evolutionarily conserved secreted-type glycoprotein belonging to the WNT family. WNT2 mRNA is expressed in human fetal lung and placenta, but almost undetectable in normal gastrointestinal tract. WNT2 mRNA is frequently up-regulated in human gastric cancer due to tumor-stromal interaction, and WNT2 gene is rarely amplified in human gastric cancer. WNT2 mRNA is also frequently up-regulated in colorectal polyps, primary colorectal cancer of stage A-C, and also in liver metastasis from colorectal cancer. Putative biding sites for estrogen receptor, GATA-1, AP-2, TCF-1, BHLH, MBF-I, p53, and HNF-5 are located within the 5'-flanking region of human WNT2 gene. WNT2 is up-regulated by beta-estradiol in human MCF-7 cells; however, the mechanism of WNT2 up-regulation in most cases of gastrointestinal cancer remains to be elucidated. WNT2 is a tumor marker of gastric and colorectal cancer. Detection of theWNT2 protein in feces by immunohistochemistry or ELISA and WNT2 mRNA in feces by cDNA-PCR or custom-made microarray could be applied for screening of colorectal cancer. Because WNT2 up-regulation leads to carcinogenesis through activation of the WNT-beta-catenin pathway, WNT2 specific antagonist might be applied for chemoprevention or treatment of gastrointestinal cancer. WNT2 gene is one of the targets for pharmacogenomics in the field of oncology.
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PMID:WNT2 and human gastrointestinal cancer (review). 1453 14

Lipid-modified soluble proteins Hedgehog (SHH, DHH and IHH) and WNT (WNT1, WNT2, WNT2B, WNT3, etc.) share distantly related mechanisms for ligand modification as well as for signaling through seven-transmembrane protein with Frizzled domain. Hedgehog and WNT signaling pathways network together during embryogenesis and carcinogenesis. Dispatched 1 (DISP1) and Dispatched 2 (DISP2) are human homologs for Drosophila Dispatched implicated in the release of lipid-anchored Hedgehog from producing cells. Here, we identified and characterized Dispatched 3 (DISP3) gene by using bioinformatics. DISP3 complete coding sequence was determined by assembling BU170953 EST and KIAA1337 uncharacterized cDNA. DISP3 gene at human chromosome 1p36.22 was linked to D1S2667 microsatellite maker and TERE1 gene, whose locus is associated with prostate cancer, bladder cancer, and liver cancer. DISP3 mRNA was expressed in human embryonic stem (ES) cells, brain, testis, lung carcinoid, neuroblastoma, retinoblastoma and brain tumor. DISPH1 domain with five transmembrane regions (codon 452-637 of DISP3) and DISPH2 domain with four transmembrane regions (codon 1116-1319 of DISP3) were identified as novel domains conserved between DISP3 (1392 aa) and DISP1. The region around DISPH1 and DISPH2 domains of DISP3 protein was the Patched homologous region conserved among Patched family members and DISP family members. Because DISP3 and DISP1 are multi-span transmembrane proteins with the Patched homologous region, DISP3 is predicted to be implicated in the release of lipid-anchored secreted proteins. This is the first report on identification and characterization of the DISP3 gene.
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PMID:Identification and characterization of DISP3 gene in silico. 1564 43


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