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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumors transplanted into nude mice using the TTK-1 cell lines [TTK-1(E) and TTK-1(F)] derived from normal human early decidual tissue were studied morphologically. The epithelial-like cell line TTK-1(E) and the fibroblast-like cell line TTK-1(F) were maintained in culture through one hundred and ten subcultures since July 1979. Rapidly growing tumor nodules formed at the implantation sites. The incidence of tumor growth was 100% for both cell lines. Histologically the tumors were composed of poorly-differentiated cells arranged in a cord-like structure and showed typical malignant characteristics. Immunohistochemical studies, electron microscopy and immunocytochemical studies revealed that the tumors from the two cell lines differed in many respects. The tumors formed by TTK-1(E) showed epithelial characteristics and the tumors formed by TTK-1(F) showed both epithelial and mesenchymal characteristics. Therefore, TTK-1(E) might be useful as an in vitro model of endometrial cancer and TTK-1(F) as an in vitro model of both endometrial cancer and endometrial stromal tumor (containing mixed mesodermal tumor). These tumors will be valuable for future studies of the tumorigenicity and therapy of uterine malignant tumors. They may reflect the various functions of decidual tissue.
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PMID:[Ultrastructural studies of tumors transplanted into nude mice using the TTK-1 cell lines derived from normal human early decidual tissue]. 247 57

Two cell lines, TTK-1(E) and TTK-1(F), derived from normal human early decidual tissue have been maintained in culture through forty subcultures since July, 1979. These cell lines were transplanted subcutaneously into nude mice at 6 weeks of age to investigate their tumorigenicity. Rapidly growing tumor nodules formed at the site of implantation. The incidence of tumor growth was 60% in TTK-1(E) and 80% in TTK-1(F). The tumor tissues were composed of poorly differentiated cells arranged in cord-like and/or gland-like structures, and showed the malignant histological characteristics. Light microscopic and electron microscopic studies revealed that the properties of the tumor cell populations are identical with those of the culture cells of the two cell lines before implantation. These results obviously indicated that the tumors had grown from the implanted cells. Although the tumors developed from the respective two cell line showed some common histological features, they apparently differed in light microscopic and electron microscopic findings. Tumorigenesis with malignant features could be attributed to the in vitro spontaneous neoplastic transformations during successive subcultures, which might be useful as an in vitro model of endometrial carcinogenesis.
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PMID:[Tumorigenicity of the cell lines (TTK-1 cell lines) derived from normal human decidua in nude mice]. 651 29

Beta-Catenin is a key regulator of the cadherin-mediated cell-cell adhesion system and an important element in the Wnt signal transduction pathway. Stabilization and accumulation of cytoplasmic beta-catenin, which result from mutations in either the adenomatous polyposis coli or beta-catenin genes, are causatively associated with colon carcinogenesis. In the present study, we examined the expression of beta-catenin in rat colon tumors induced by azoxymethane in comparison with adjacent normal colon mucosa by immunostaining and immunoblotting. Cytoplasmic and nuclear immunostaining was pronounced in all colon adenoma and carcinoma tissues, whereas antibody binding was limited to membranes at the intercellular borders in normal colon epithelial cells. Increase of the free beta-catenin fraction in tumor cells was also indicated by immunoblot analysis of fractionated tissue lysates. Investigation of mutations in the glycogen synthase kinase-3beta phosphorylation consensus motif of the beta-catenin gene by PCR-single strand conformation polymorphism methods and direct sequencing revealed eight mutations in six of the eight colon carcinomas, and seven of these were shown to be G:C to A:T transitions, with five being CTGGA to CTGAA. Such frequent mutations of the beta-catenin gene in azoxymethane-induced rat colon tumors suggest that consequent alterations in the stability and localization of the protein may play an important role in this colon carcinogenesis model.
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PMID:Beta-catenin is frequently mutated and demonstrates altered cellular location in azoxymethane-induced rat colon tumors. 942 55

The beta-catenin, glycogen synthase kinase 3beta (GSK-3beta), and adenomatous polyposis coli (APC) gene products interact to form a network that influences the rate of cell proliferation. Medulloblastoma occurs as part of Turcot's syndrome, and patients with Turcot's who develop medulloblastomas have been shown to harbor germ-line APC mutations. Although APC mutations have been investigated and not identified in sporadic medulloblastomas, the status of the beta-catenin and GSK-3beta genes has not been evaluated in this tumor. Here we show that 3 of 67 medulloblastomas harbor beta-catenin mutations, each of which converts a GSK-3beta phosphorylation site from serine to cysteine. The beta-catenin mutation seen in the tumors was not present in matched constitutional DNA in the two cases where matched DNA was available. A loss of heterozygosity analysis of 32 medulloblastomas with paired normal DNA samples was performed with four microsatellite markers flanking the GSK-3beta locus; loss of heterozygosity with at least one marker was identified in 7 tumors. Sequencing of the remaining GSK-3beta allele in these cases failed to identify any mutations. Taken together, these data suggest that activating mutations in the beta-catenin gene may be involved in the development of a subset of medulloblastomas. The GSK-3beta gene does not appear to be a target for inactivation in this tumor.
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PMID:Sporadic medulloblastomas contain oncogenic beta-catenin mutations. 950 Apr 46

Mutation of the adenomatous polyposis coli (APC) tumor suppressor gene initiates the majority of colorectal (CR) cancers. One consequence of this inactivation is constitutive activation of beta-catenin/Tcf-mediated transcription. To further explore the role of the APC/beta-catenin/Tcf pathway in CR tumorigenesis, we searched for mutations in genes implicated in this pathway in CR tumors lacking APC mutations. No mutations of the gamma-catenin (CTNNG1), GSK-3alpha (GSK3A), or GSK-3beta (GSK3B) genes were detected. In contrast, mutations in the NH2-terminal regulatory domain of beta-catenin (CTNNB1) were found in 13 of 27 (48%) CR tumors lacking APC mutations. Mutations in the beta-catenin regulatory domain and APC were observed to be mutually exclusive, consistent with their equivalent effects on beta-catenin stability and Tcf transactivation. In addition, we found that CTNNB1 mutations can occur in the early, adenomatous stage of CR neoplasia, as has been observed previously with APC mutations. These results suggest that CTNNB1 mutations can uniquely substitute for APC mutations in CR tumors and that beta-catenin signaling plays a critical role in CR tumorigenesis.
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PMID:Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. 951 95

Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator downstream of the Wnt signaling pathway. Activation of the pathway by stabilization of beta-catenin has been shown to be important in the development of colorectal carcinoma, which is mainly caused by inactivating mutations of the adenomatous polyposis coli tumor suppressor gene or by activating mutations in exon 3 of the beta-catenin gene. Here, we analyzed mutations in exon 3 of the beta-catenin gene in endometrial carcinoma cases in which loss of heterozygosity at the adenomatous polyposis coli tumor suppressor gene locus has been rarely reported. We found that 10 of 76 cases had beta-catenin gene mutations. All mutations identified were single-base missense mutations on serine/threonine residues (codons 33, 37, 41, and 45), altering the glycogen synthase kinase-3beta phosphorylation consensus motif, which participates in the degradation of beta-catenin. To determine whether these beta-catenin mutations actually led to stabilization of this protein, expression of beta-catenin was analyzed immunohistochemically, and 9 of 10 cases with the beta-catenin mutation and 20 of 66 cases without it showed accumulation of beta-catenin in the cytoplasm and/or nucleus. In total, 38% of cases showed accumulation of beta-catenin. These data indicate that stabilization of beta-catenin due to mutations in exon 3 of the beta-catenin gene and other mechanisms may have an important role in development of endometrial carcinomas.
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PMID:Beta-catenin mutation in carcinoma of the uterine endometrium. 972 53

Conductin or Axil, an Axin homolog, plays an important role in the regulation of beta-catenin stability in the Wnt signaling pathway. To facilitate the molecular analysis of the human gene, we isolated the human homolog, AXIN2. The cDNA contains a 2529-bp open reading frame and encodes a putative protein of 843 amino acids. Compared with rat and mouse homologs, AXIN2 shows an overall 89% amino acid identity. Several functional domains in this protein are highly conserved including the GRS (95.9%), GSK-3beta (96.3%), Dsh (98%), and beta-catenin (89.9%) domains. Radiation hybrid mapping localized the AXIN2 gene to human chromosome 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Human AXIN2 is thus a very strong candidate involved in multiple tumor types.
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PMID:Cloning of the human homolog of conductin (AXIN2), a gene mapping to chromosome 17q23-q24. 1004 90

beta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex. Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta and APC. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with FWD1. FWD1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. In contrast, a dominant-negative mutant form of FWD1 inhibited the ubiquitination process and stabilized beta-catenin. These results suggest that the Skp1/Cullin/F-box protein FWD1 (SCFFWD1)-ubiquitin ligase complex is involved in beta-catenin ubiquitination and that FWD1 serves as an intracellular receptor for phosphorylated beta-catenin. FWD1 also links the phosphorylation machinery to the ubiquitin-proteasome pathway to ensure prompt and efficient proteolysis of beta-catenin in response to external signals. SCFFWD1 may be critical for tumor development and suppression through regulation of beta-catenin protein stability.
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PMID:An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. 1022 55

The tumor suppressor function of the adenomatous polyposis coli protein (APC) depends, in part, on its ability to bind and regulate the multifunctional protein, beta-catenin. beta-Catenin binds the high mobility group box transcription factors, lymphocyte enhancer-binding factor (LEF) and T-cell factor, to directly regulate gene transcription. Using LEF reporter assays we find that APC-mediated down-regulation of beta-catenin-LEF signaling is reversed by proteasomal inhibitors in a dose-dependent manner. APC down-regulates signaling induced by wild type beta-catenin but not by the non-ubiquitinatable S37A mutant, beta-catenin. Bisindoylmaleimide-type protein kinase C inhibitors, which prevent beta-catenin ubiquitination, decrease the ability of APC to down-regulate beta-catenin-LEF signaling. All these effects on LEF signaling are paralleled by changes in beta-catenin protein levels. Lithium, an inhibitor of glycogen synthase kinase-3beta, does not alter the ability of APC to down-regulate beta-catenin protein and beta-catenin-LEF signaling in the colon cancer cells that were tested. These results point to a role for beta-catenin ubiquitination, proteasomal degradation, and potentially a serine kinase other than glycogen synthase kinase-3beta in the tumor-suppressive actions of APC.
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PMID:The ubiquitin-proteasome pathway and serine kinase activity modulate adenomatous polyposis coli protein-mediated regulation of beta-catenin-lymphocyte enhancer-binding factor signaling. 1034 31

Mutations in the APC gene contribute to development of sporadic desmoid tumors as well as to the hereditary tumors that usually accompany familial adenomatous polyposis (FAP). Adenomatous polyposis coli (APC) mutations cause an intracellular accumulation of beta-catenin that results in abnormal signaling in the wnt/wingless pathway. Mutations of the beta-catenin gene itself have also been noted in several types of tumors. In this study we screened the beta-catenin gene in 13 sporadic desmoid tumors for alterations in exon 3, which encodes several serine/threonine residues that are targets for phosphorylation by GSK-3beta. Somatic substitutions at codons 41 (threonine) and 45 (serine) were identified in seven independent tumors, respectively. Although no APC mutations were detected among the remaining six tumors, we found accumulation of beta-catenin by Western blotting analysis in one such tumor for which frozen tissues were available. Our results have suggested that possible involvement of beta-catenin activation by beta-catenin gene mutation or alteration of other factor(s) can contribute to desmoid tumorigenesis.
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PMID:Frequent mutations in the beta-catenin gene in desmoid tumors from patients without familial adenomatous polyposis. 1036 40


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