Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cadherins, calcium-dependent cell adhesion molecules, play crucial roles, not only in the maintenance of tissue integrity, but also in the regulation of many aspects of cell behavior. We investigated the expression of "classic" E-, N- and P-cadherins in bone marrow-derived cultured mast cells (BMMC) and peritoneal mast cells (PMC) from mice. Flow cytometric analysis and immunocytochemical staining indicated that E-cadherin was expressed on the cell surface of BMMC and also at lower levels on PMC. N-cadherin was also expressed on the surface of BMMC, but not of PMC, whereas P-cadherin expression was seen in neither cell type. Significant expression of E- and N-cadherin mRNA was observed in BMMC by reverse transcriptase-polymerase chain reaction (RT-PCR), but PMC expressed only E-cadherin mRNA. Western blotting analysis indicated expression of alpha- and beta-catenins and p120-catenin (or p120 cas) in BMMC, whereas PMC showed less intense expression of alpha- and beta-catenins with high levels of p120 expression. Analyses of beta-catenin or E-cadherin immunoprecipitates from BMMC lysate revealed that alpha-catenin, beta-catenin, and E-cadherin were co-precipitated, suggesting that E-cadherin and catenins form a complex in mast cells. Addition of a blocking antibody of homophilic E-cadherin interactions, or a synthetic E-cadherin-binding decapeptide containing the histidine-alanine-valine (HAV) sequence in methylcellulose cultures of gut intraepithelial mononuclear cells or BMMC, significantly suppressed the clonal growth of mast cells. Furthermore, the blocking antibody or synthetic decapeptide significantly suppressed BMMC adhesion to E-cadherin-expressing F9 cell monolayers. These results indicated that E-cadherin and associated cytoplasmic proteins in mast cells might be involved in the regulation of certain stages of mast cell differentiation and cell-cell interactions.
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PMID:E-cadherin and cadherin-associated cytoplasmic proteins are expressed in murine mast cells. 1104 74

E-cadherin is one of the cell adhesion molecules normally expressed on epithelial cells. We previously reported that murine bone marrow-derived mast cells express E-cadherin that could be involved in homophilic binding with epithelial cell E-cadherin. In the present study we examined whether E-cadherin is also expressed in human mast cell HMC-1. Gene expression of E-cadherin and beta-catenin was observed in HMC-1 by reverse transcription-polymerase chain reaction (RT-PCR), while N-cadherin expression was undetectable. cDNA sequencing of HMC-1 E-cadherin revealed no deletions or mutations. E-cadherin expression in HMC-1 was confirmed by immunoblotting as well as by flow cytometric analyses. In the presence of E-cadherin blocking antibody or a synthetic E-cadherin decapeptide with HAV sequence in culture medium, adhesion of HMC-1 cells to the A431 epithelial cell monolayer was slightly but significantly suppressed. In contrast, N- or P-cadherin decapeptides did not suppress the binding. These results indicated that human mast cell HMC-1 expresses E-cadherin, and is possibly involved in cellular interactions with epithelial cells, while other functions still remain to be elucidated.
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PMID:Expression of E-cadherin in human mast cell line HMC-1. 1462 73

Communication between nerves and mast cells is a prototypic demonstration of neuro-immune interaction. Numerous studies have shown that the stimulation of nerves (or addition of neurotransmitters) can evoke activation of mast cells, and that mast cell-derived mediators can influence neuronal activity. However, the molecules involved in the membrane-membrane contacts between nerves and mast cells are still unknown. Here, we used an in vitro co-culture approach comprising interaction between immune (bone marrow-derived mast cell, BMMC) and nerve cells (superior cervical ganglia, SCG). The experiments showed clearly that the nerve-mast cell communication was supported by synapse-like structure and that N-cadherin, not E-cadherin, played an essential role in the synapse-like structure. In addition, we found that the synapse-like structure was assisted by clustering of beta-catenin to N-cadherin.
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PMID:N-cadherin plays a role in the synapse-like structures between mast cells and neurites. 1557 1

Gardner fibroma (GAF) is a benign soft tissue lesion with a predilection for childhood and adolescence and an association with familial adenomatous polyposis (FAP) and desmoid type fibromatosis (desmoid). We report 45 patients with GAF with clinicopathologic correlation and immunohistochemical analysis for beta-catenin and related proteins. Forty-five patients with 57 GAFs were identified from surgical pathology and consultation files. Immunohistochemistry for beta-catenin, cyclin-D1, and C-myc was performed on formalin-fixed, paraffin-embedded tissues using standard techniques in 25 GAFs from 24 patients. Information about family history, intestinal polyps, colon cancer, and soft tissue tumors was available in 23 patients. Sixty-nine percent had known FAP or adenomatous polyposis coli (APC), 22% had no history of familial polyps or soft tissue tumors, and 13% had an individual or family history of soft tissue masses and/or desmoids, with follow-up periods of 6 months to 26 years (median 3 y, mean 5 y). The age range at initial diagnosis was 2 months to 36 years. Seventy-eight percent were diagnosed in the first decade, 15% in the second decade, and 7% in the third decade. Eight patients (18%) had documented desmoids concurrently or later; 4 of these had FAP and 1 had familial desmoids. Sites of GAF included the back and paraspinal region in 61%, the head and neck in 14%, the extremities in 14%, and the chest and abdomen in 11%. All displayed a bland hypocellular proliferation of haphazardly arranged coarse collagen fibers with a bland hypocellular proliferation of inconspicuous spindle cells, small blood vessels, and a sparse mast cell infiltrate. Immunohistochemically, 64% showed nuclear reactivity for beta-catenin (9 patients with known APC, 5 without definite information about FAP). One hundred percent showed nuclear reactivity for both cyclin-D1 and C-myc. beta-catenin reactivity had no correlation with age, site, or recurrence. Two beta-catenin-negative GAFs were from FAP patients. In conclusion, GAF has a predilection for childhood and early adulthood, a strong association with FAP/APC, an association with concurrent or subsequent development of desmoids, and overexpression of beta-catenin and other proteins in the APC and Wnt pathways. The proportion of sporadic GAFs that have APC mutation remains to be determined.
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PMID:Gardner fibroma: a clinicopathologic and immunohistochemical analysis of 45 patients with 57 fibromas. 1732 83

The role of mast cells in tumor growth is still controversial. In this study we analyzed the effects of both histamine and pre-formed mediators spontaneously released by mast cells on the growth of two human hepatocellular carcinoma cell lines, HA22T/VGH and HuH-6, with different characteristics of differentiation, biological behavior and genetic defects. We showed that total mast cell releasate, exocytosed granules (granule remnants) and histamine reduced cell viability and proliferation in HuH-6 cells. In contrast, in HA22T/VGH cells granule remnants and histamine induced a weak but significant increase in cell growth. We showed that both cell lines expressed histamine receptors H(1) and H(2) and that the selective H(1) antagonist terfenadine reverted the histamine-induced inhibition of HuH-6 cell growth, whereas the selective H(2) antagonist ranitidine inhibited the histamine-induced cell growth of HA22T/VGH cells. We demonstrated that histamine down-regulated the expression of beta-catenin, COX-2 and survivin in HuH-6 cells and that this was associated with caspase-3 activation and PARP cleavage. On the contrary, in HA22T/VGH cells expression of survivin and beta-catenin increased after treatment with granule remnants and histamine. Overall, our results suggest that mediators stored in mast cell granules and histamine may affect the growth of liver cancer cells. However, mast cells and histamine may play different roles depending on the tumor cell features. Finally, these data suggest that histamine and histamine receptor agonists/antagonists might be considered as "new therapeutic" drugs to inhibit liver tumor growth.
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PMID:Histamine and spontaneously released mast cell granules affect the cell growth of human hepatocellular carcinoma cells. 1760 79

Gain-of-function mutations in the proto-oncogene c-kit that induce constitutive kinase activity of its product, KIT protein, are characteristic of human mast cell disease and are believed to play a central role in mast cell leukemia oncogenesis, proliferation and survival. Nuclear overexpression of the Wnt effector beta-catenin and deregulated beta-catenin nuclear signaling can promote malignant transformation in solid tumors and hematologic malignancies. However, a role for beta-catenin in mast cell leukemia has not been described. Nuclear accumulation of beta-catenin is upregulated by its tyrosine phosphorylation, a process that can be exacerbated by deregulated expression of oncogenic tyrosine kinases. Here, we investigated the relationship between activated KIT and beta-catenin signaling in mast cell leukemia. Beta-catenin was tyrosine-phosphorylated in cells with KIT activated by either gain-of-function mutation or incubation with the KIT ligand stem cell factor. Beta-catenin tyrosine phosphorylation depended on KIT activity but not on PI3K-AKT activation. Tyrosine phosphorylation of beta-catenin was associated with its nuclear localization and enhanced transcription of target genes c-myc and cyclin D1. Endogenous KIT and beta-catenin were found to associate in mast cell leukemia cells, and in vitro kinase assay demonstrated that active KIT phosphorylates tyrosine residues of beta-catenin directly. Aberrant beta-catenin-driven transcription caused by deregulated KIT may represent a significant new target for treatment of mast cell leukemia.
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PMID:KIT regulates tyrosine phosphorylation and nuclear localization of beta-catenin in mast cell leukemia. 1794 10