Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour necrosis factor alpha (TNF-alpha) is a cytokine with pleiotropic effects on cells ranging from proliferation to apoptosis. These biological effects of TNF-alpha are believed to be elicited by the induction or enhancement of the expression of TNF-alpha responsive genes in the target cells. TNF-alpha is pro-inflammatory and a principal mediator in the pathogenesis of arthritis. The activation of an inflammatory cascade by TNF-alpha in arthritis results in the degradation of cartilage, joint destruction and loss of function. Because TNF-alpha is an important mediator in the pathogenesis of arthritis, the present study addresses the identification of novel TNF-alpha responsive genes in HTB-94 cell line which is of human origin and maintains a chondrocytic phenotype. The three identified cDNAs were previously not known to be induced or upregulated by TNF-alpha in chondrocytes or cells of chondrocytic lineage. One of the identified cDNAs had sequence similarity to human hydroxyl lyase mRNA (PLOD), an enzyme involved in collagen biosynthesis and its metabolism; the second cDNA had sequence similarity to the human cytoplasmic anti-proteinase-2 mRNA (CAP-2), a member of a group of proteins shown to be associated with protecting cells from TNF-alpha-induced apoptosis; and the third cDNA had sequence similarity to a dual specificity kinase, TTK, which is associated with cell proliferation. Relative gene expression level analysis by PCR and by Northern blotting revealed that treatment with TNF-alpha enhanced the expression of PLOD, CAP2 and TTK transcripts which confirmed the results obtained with display gels. Furthermore, TTK mRNA expression was also induced in human articular chondrocytes treated with TNF-alpha but not in untreated chondrocytes. Our results suggest that these genes may play a role in chondrocytic responses to TNF-alpha-mediated stimuli affecting the cartilage homeostasis.
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PMID:Tumour necrosis factor alpha enhances the expression of hydroxyl lyase, cytoplasmic antiproteinase-2 and a dual specificity kinase TTK in human chondrocyte-like cells. 1067 Dec 99

Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p < 0.05) overexpressed in tumor tissue compared with healthy colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells.
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PMID:Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications. 2763 8

The aim of this study was to determine the expression levels of TTK in clear cell renal cell carcinoma (ccRCC) tissues and its possible link with the clinical pathologic characteristics and the prognosis of patients suffering this disease, and to further explore the potential role of TTK in the progression of ccRCC. Immunohistochemical (IHC) assays were performed to detect the expression levels of TTK in 112 samples of ccRCC tissues and corresponding non-tumor tissues. According to the results of IHC assays, patients were divided into TTK high expression and low expression group. Clinical analysis related to the clinical features (age, gender, T stage), and the potential link between TTK expression levels and clinical features were analyzed. In addition, the effects of TTK on the proliferation and invasion of ccRCC cells were detected through colony formation assay and transwell assays, respectively. The possible effects of TTK on tumor growth and metastasis were measured in mice. We found a high expression level of TTK in human ccRCC tissues from patients who received surgical treatment. We also found its expression level was obviously associated with clinical characteristics, such as T stage (p=0.008) and lymphatic metastasis (p=0.023). We further confirmed that knockdown of TTK suppressed cell proliferation and invasion in 2 types of ccRCC cells, HTB-47 and CRL-1932 cells. Furthermore, TTK contributes to tumor growth and metastasis of ccRCC in mice. We found that TTK affected the progression of ccRCC and further mechanically confirmed it could be a novel therapeutic target for ccRCC treatment.
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PMID:TTK contributes to tumor growth and metastasis of clear cell renal cell carcinoma by inducing cell proliferation and invasion. 3160 31