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

Human WNT10A and WNT6 were cloned and characterized. WNT10A encoded a 417-amino-acid polypeptide with WNT core domain, and WNT6 encoded a 365-amino-acid polypeptide with N-terminal signal peptide, WNT core domain, and RGD motif. WNT10A and WNT6 genes were clustered in the head-to-tail manner with an interval less than 7.0 kb in human chromosome 2q35 region. Among human WNT family, WNT10A was most homologous to WNT10B (59.2% amino-acid identity), and WNT6 was most homologous to WNT1 (47.4% amino-acid identity). WNT10B and WNT1 genes were also clustered in human chromosome 12q13 region. Two WNT gene clusters in human chromosome 2q35 and 12q13 regions might be generated due to duplication of ancestral gene cluster. The 3.0- and 2.4-kb WNT10A mRNAs were expressed in fetal kidney, placenta, adult spleen and kidney. The 2.0-kb WNT6 mRNA was coexpressed with WNT10A in placenta and adult spleen. WNT10A and WNT6 were strongly coexpressed in SW480 (colorectal cancer). In addition to SW480, WNT10A was strongly expressed in HL-60 (promyelocytic leukemia) and Raji (Burkitt's lymphoma), and WNT6 in HeLa S3 (cervical cancer). Overexpression WNT10A and WNT6 might play key roles in human carcinogenesis through activation of WNT-beta-catenin-TCF signaling pathway, just like Wnt10b and Wnt1.
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PMID:WNT10A and WNT6, clustered in human chromosome 2q35 region with head-to-tail manner, are strongly coexpressed in SW480 cells. 1135 55

WNT signaling pathway is implicated in carcinogenesis and embryogenesis. We have previously cloned and characterized WNT10A and WNT6, which are clustered in human chromosome 2q35 region. In this study, we investigated expression of WNT10A and WNT6 in gastric cancer. The 3.0- and 2.4-kb WNT10A mRNAs were expressed in gastric cancer cell lines MKN7, MKN45 and MKN74. The 2.0-kb WNT6 mRNA was expressed in gastric cancer cell lines MKN28 and MKN74. WNT10A was up-regulated in 3 out of 6 cases of primary gastric cancer, while WNT6 was not up-regulated in primary gastric cancer. Effects of inflammatory cytokines and Helicobacter pylori (H. pylori) on expression of WNT10A and WNT6 were next investigated. Interferon gamma (IFNgamma) failed to induce up-regulation of WNT10A and WNT6. Tumor necrosis factor alpha (TNFalpha) induced up-regulation of WNT10A in MKN45 cells. Up-regulation of WNT10A reached maximum at 6 h after TNFalpha treatment. H. pylori also induced up-regulation of WNT10A in MKN45 cells. These results strongly suggest that up-regulation of WNT10A induced by TNFalpha and H. pylori might play key roles in human gastric cancer through activation of WNT--beta-catenin--TCF signaling pathway.
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PMID:Up-regulation of WNT10A by tumor necrosis factor alpha and Helicobacter pylori in gastric cancer. 1149 32

WNT signaling pathway is implicated in carcinogenesis and embryogenesis. We have previously cloned and characterized WNT10A, and demonstrated up-regulation of WNT10A in gastric cancer. Here, we investigated expression of WNT10A mRNA in various types of human cancer. WNT10A mRNA was detected in 10 out of 12 esophageal cancer cell lines by cDNA-PCR, and was significantly up-regulated in esophageal cancer cell lines TE2, TE3, TE4, and a brain tumor cell line A-172. WNT10A mRNA was not up-regulated by retinoic acid in a teratocarcinoma cell line NT2. TFF1/pS2 mRNA, but not WNT10A mRNA, was up-regulated by beta-estradiol in a breast cancer cell line MCF-7. Expression of WNT10A mRNA in various types of primary cancers was next investigated by using Matched tumor/normal expression array filter. WNT10A mRNA was significantly up-regulated in 2 out of 8 cases of primary gastric cancer, and in 1 out of 7 cases of primary rectal cancer. Expression of WNT10A mRNA in esophageal cancer was not investigated, because such samples were not blotted on the expression array filter. Up-regulation of WNT10A mRNA might play key roles in some cases of esophageal, gastric, and colorectal cancer.
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PMID:Expression of WNT10A in human cancer. 1160

WNT signaling pathway is implicated in carcinogenesis. Here, we cloned and characterized human WNT11, which showed three amino-acid substitutions (Ala121Thr, Gly156Arg, and Ser271Trp) compared with human WNT11 cDNA previously isolated by another group. WNT11 encoded a 354 amino-acid polypeptide with five N-glycosylation sites. Gly156 of human WNT11 was conserved in other members of the human WNT family, such as WNT2B1, WNT2B2, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT10A, and WNT14. The Ala121-Gly156-Ser271 WNT11 allele isolated in this study was also identified in human genome draft sequence AC069055. Expression profile of WNT11 was next investigated. The 4.3-kb WNT11 mRNA was expressed in fetal lung, kidney, adult heart, liver, skeletal muscle, and pancreas. WNT11 mRNA was significantly up-regulated in a gastric cancer cell line MKN45 and a cervical cancer cell line SKG-IIIa. Among various types of human primary tumors, WNT11 mRNA was up-regulated in four cases of colorectal adenocarcinoma, and a case of renal cell carcinoma. Up-regulation of WNT11 mRNA might play an important role in human carcinogenesis through activation of the WNT signaling pathway.
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PMID:Molecular cloning and characterization of human WNT11. 1171 81

WNT10A and WNT10B genes are human orthologues of mouse proto-oncogene Wnt-10b. We have previously cloned and characterized WNT10A, and demonstrated up-regulation of WNT10A by tumor necrosis factor alpha (TNFalpha) in gastric cancer. Here, we cloned and characterized human WNT10B, which showed Gly60Asp amino-acid substitution compared with human WNT10B previously reported by another group. Gly60 WNT10B allele was identified in 2 human genome draft sequences and 7 human ESTs, while Asp60 WNT10B allele was not identified in any human genome draft sequences or ESTs. The Gly60-type WNT10B cDNA isolated in this study might be derived from more common WNT10B allele. WNT10B was most homologous to WNT10A (64.5% total amino-acid identity) among human WNTs. Variable region in the WNT core domain of WNT10B and WNT10A were longer than that of other WNTs, such as WNT2B1, WNT2B2, WNT3, WNT3A, WNT5B, WNT7B, WNT8A, WNT11, WNT14, and WNT14B/WNT15. We next investigated expression of WNT10B in human gastric cancer. WNT10B was moderately expressed in MKN45 and MKN74 cells, and weakly expressed in Okajima, TMK1, MKN7, MKN28, and KATO-III cells. Because interferon gamma (IFNgamma) and TNFalpha were frequently elevated in gastric mucosa with Helicobacter pylori infection, effects of IFNgamma and TNFalpha on WNT10B expression in MKN45 cells were investigated. TNFalpha induced transient up-regulation of WNT10B mRNA in MKN45 cells. Up-regulation of WNT10B in human gastric mucosa might lead to gastric carcinogenesis through activation of the beta-catenin - TCF signaling pathway, just like up-regulation of Wnt-10b in mouse mammary gland leads to mammary carcinogenesis.
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PMID:Proto-oncogene WNT10B is up-regulated by tumor necrosis factor alpha in human gastric cancer cell line MKN45. 1171 88

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

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

Mouse mammary tumor virus (MMTV) is a retrovirus, activating Wnt genes (Wnt1/int-1, Wnt3/int-4, Wnt10b), Fgf genes (Fgf3/int-2, Fgf4, Fgf8) and other genes (Notch4/int-3, Eif3s6/int-6) due to proviral integration. Among 19 WNT genes, WNT3 and WNT14B genes are clustered in human chromosome 17q21, WNT3A and WNT14 in human chromosome 1q42, WNT10A and WNT6 in human chromosome 2q35, and WNT10B and WNT1 in human chromosome 12q13. Among 22 FGF genes, FGF19, FGF4 and FGF3 genes are clustered in human chromosome 11q13, while FGF23 and FGF6 in human chromosome 12p13. WNT and FGF gene clusters are conserved between the human genome and the mouse genome. Activation of mouse Wnt or Fgf genes due to proviral integration of MMTV occurs in 5 out of 13 clustered genes, and in 1 out of 28 solitary genes (p=0.0033), which clearly indicates that mouse Wnt or Fgf gene clusters are recombination hot spots associated with carcinogenesis. Recombination results in retroviral integration as well as in chromosomal translocation, gene amplification and deletion during carcinogenesis. The CCND1-FGF19-FGF4-FGF3 gene cluster in human chromosome 11q13 is amplified in breast cancer, squamous cell carcinoma of head and neck, and bladder tumors, and is also translocated in parathyroid tumors and B-cell lymphoma. WNT gene clusters on human chromosome 1q42, 2q35, 12q13, and 17q21 as well as FGF gene cluster on human chromosome 12p13 might be amplified or translocated in human cancer just like FGF gene cluster on human chromosome 11q13.
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PMID:WNT and FGF gene clusters (review). 1242 77

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


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