Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fas receptor is a member of a superfamily of receptors characterized by cysteine-rich motifs in the extracellular domain of the molecule. Binding of Fas ligand to Fas receptor leads to activation of the latter and the induction of intracellular signals that result in apoptotic cell death. In the present study, we used reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis to examine the expression of mRNAs and proteins of Fas receptor and Fas ligand in human oral squamous carcinoma SCC-25 cells treated with okadaic acid. The PCR product of Fas receptor mRNA was detected in the cells and a protein with an estimated molecular weight of 35,000 was also expressed in them. Expression of Fas receptor mRNA stimulated by okadaic acid was elevated in dose- and time-dependent manners as judged by semiquantitative RT-PCR analysis, with the maximum expression level at 50 nM and 8 h treatment. Fas ligand mRNA expression was also stimulated by okadaic acid in SCC-25 cells in dose- and time-dependent manners. Okadaic acid also stimulated the expression of Fas ligand protein in the cells. Okadaic acid in serum-free medium induced apoptosis in SCC-25 cells in a time-dependent manner up to 24 h as determined by nuclear condensation and fragmentation of chromatin and DNA ladder formation. The present results indicate that the expression of Fas receptor and Fas ligand is negatively regulated by a protein phosphatase(s) sensitive to okadaic acid and is involved in okadaic acid-induced apoptosis in SCC-25 cells. Our results also suggest that Fas receptor and Fas ligand system might regulate apoptosis in SCC-25 cells in an autocrine fashion.
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PMID:Okadaic acid stimulates apoptosis through expression of Fas receptor and Fas ligand in human oral squamous carcinoma cells. 1175 16

Studies assessed if the serine/threonine protein phosphatase-2A (PP-2A) maintains cytoskeletal integrity of normal keratinocytes and if this differs in malignant cells. Murine and human keratinocyte cell lines contained more PP-2A activity than did the murine SCC VII/SF squamous cell carcinoma cells or primary cultures of human head and neck squamous cell carcinoma (HNSCC) cells. Since tyrosine phosphorylation of the focal adhesion proteins paxillin and FAK is indicative of more stable focal adhesions, cells were immunostained for phosphotyrosine plus either paxillin or FAK, and then examined by confocal microscopy. In non-malignant keratinocytes, phosphotyrosine staining co-localized with paxillin and FAK. This co-localization occurred at the cell periphery in a pattern resembling focal adhesions. In contrast, the co-localization of phosphotyrosine with either paxillin or FAK along the cell periphery was almost absent in the SCC cells or in keratinocytes that were treated with okadaic acid to inhibit PP-2A activity. Consistent with this was a rounded cellular morphology with less extended processes as compared to control keratinocytes. These studies indicate PP-2A maintains the organization and tyrosine-phosphorylated state of the focal adhesion proteins FAK and paxillin, and that the loss of PP-2A activity results in a loss of cytoskeletal organization, as is seen in SCC.
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PMID:Protein phosphatase-2A maintains focal adhesion complexes in keratinocytes and the loss of this regulation in squamous cell carcinomas. 1555 94

Cyclosporine (CSA) is a widely used immunosuppressive agent, predominantly for transplant patients. It is well recognized that transplant patients are prone to develop squamous carcinoma of the skin and mucosa, and this high incidence of squamous carcinoma in the transplant population cannot be explained by immunosuppression alone. We hypothesize that CSA may play a significant role in the transformation of normal epidermal squamous cells to carcinoma. CSA is a specific ligand for calcineurin, a ubiquitously expressed cellular serine/threonine phosphatase, that plays important roles in the immune system and cardiac muscles. Using global gene-profiling methods, we studied the short-time CSA effect on the squamous cell line (SCC-015) using Affymetrix human gene chips (Human U133, 2.0 plus chip). Multiple groups of genes were identified to be responsive to CSA treatment, including many genes of unknown functions. We then used reverse transcriptase-polymerase chain reaction and immunoblot analyses to selectively confirm the results from the chips analyses with emphasis on the regulatory molecules important for cellular functions of apoptosis, DNA damage repair, and cellular transformation. This global gene-profiling study indicated that CSA not only functions as an immunosuppressant on the immune system, but also activates/inhibits a wide array of genes important for cell-cycle regulation, apoptosis, and oncogene/tumor-suppressor activation. These functions of CSA on skin and mucosa systems at the molecular level are likely important in the pathogenesis of squamous carcinoma in transplant patients.
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PMID:Molecular basis of posttransplant squamous cell carcinoma: the potential role of cyclosporine a in carcinogenesis. 1665 84

It has been previously shown that Walker 256 tumor cells express a high content of the anti-apoptotic protein Bcl-2 which protects mitochondria against the damaging effects of Ca(2+). In the present study, we analyze H(2)O(2)-induced apoptotic death in two different types of tumor cells: Walker 256 and SCC-25. Treatment with H(2)O(2) (4mM) increased reactive oxygen species generation and the concentration of cytosolic free Ca(2+). These alterations preceded apoptosis in both cell lines. In Walker cells, which show a high Bcl-2/Bax ratio, apoptosis was dependent on calcineurin activation and independent of changes in mitochondrial membrane potential (DeltaPsi(m)), as well as cytochrome c release. In contrast, in SCC-25 cells, which show a lower Bcl-2/Bax ratio, apoptosis was preceded by a decrease in DeltaPsi(m), mitochondrial permeability transition, and cytochrome c release. Caspase-3 activation occurred in both cell lines. The data suggest that although the high Bcl-2/Bax ratio protected the mitochondria of Walker cells from oxidative stress, it was not sufficient to prevent apoptosis through calcineurin pathways.
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PMID:High Bcl-2/Bax ratio in Walker tumor cells protects mitochondria but does not prevent H2O2-induced apoptosis via calcineurin pathways. 1743 54