Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies have shown that treatment of MCF-7 breast cancer cells with cytokine oncostatin M (OM) results in a growth arrest and a concurrent decrease in p53 expression. It remains to be determined whether these two important events are directly connected, as changes in p53 protein levels can lead to variable biological outcomes. In this study we have generated stable cell lines (MCF7-ptsp53) that express p53Val135 a p53 temperature-sensitive mutant. We demonstrate that overexpression of the wildtype (wt) p53 at permissive temperature in MCF7-ptsp53 cells leads to growth arrest at the G2-M phase of the cell cycle. Inhibition of endogenous p53 function with the expression of mutant p53 protein at non-permissive temperature did not affect the OM-induced G1 cell cycle arrest. Microarray studies were further carried out to identify p53- and OM-regulated genes that mediate the G2/M or G1 cell cycle arrest. We show that the expression of p21 was upregulated and expressions of cdc2, cyclin B2 and protein regulator of cytokinesis 1 (PRC1) were suppressed by overexpression of the wt p53 in MCF7-ptsp53 cells at the permissive temperature. In contrast, OM treatment caused coordinate changes of mRNA expression of several cell cycle components including c/EBPdelta, cdc20, and thymidine kinase 1 (TK1) that mainly affect G1-S phase transition. All together, our results suggest that the downregulation of p53 transcription may be involved in some other cellular changes induced by OM but it is not directly connected to the antiproliferative activity of OM per se.
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PMID:Molecular characterization of oncostatin M-induced growth arrest of MCF-7 cells expressing a temperature-sensitive mutant of p53. 1288 96

The mortality rate associated with hepatocellular carcinoma (HCC) is the third highest among all digestive system tumors. However, the causes of HCC development and the underlying mechanisms have remained to be fully elucidated. In the present bioinformatics study, genetic markers were identified and their association with HCC was determined. The mRNA expression datasets GSE87630, GSE74656 and GSE76427 were downloaded from the Gene Expression Omnibus (GEO) database. A total of 96 differentially expressed genes (DEGs) were screened from the 3 GEO datasets, including 25 upregulated and 71 downregulated genes. DEGs were uploaded to the database for Annotation, Visualization and Integrated Discovery to screen for enriched Gene Ontology terms in various categories and the Search Tool for the Retrieval of Interacting Genes/Proteins was used to identify the interactions and functions of the DEGs. A total of 3 genetic markers were identified in a stepwise pathway and functional analysis in a previous study. The association of the genetic markers with prognosis was analysed using the UALCAN online analysis tool. Regression analysis was also performed to identify the relationship between HCC grade and disease recurrence and the expression of genetic markers using The Cancer Genome Atlas HCC dataset. In addition, the expression of the 3 genetic markers in HCC tissues was determined using reverse transcription-quantitative PCR, the Oncomine database and the Human Protein Atlas database. The expression levels of the 3 genetic markers cyclin B2 (CCNB2), nucleolar and spindle-associated protein 1 (NUSAP1) and thymidine kinase 1 (TK1) were significantly correlated with each other and high mRNA expression of CCNB2 was significantly associated with poor overall survival of patients with HCC. Receiver operating characteristic curve analysis indicated that NUSAP1 and TK1 were capable of distinguishing between recurrent and non-recurrent HCC. Furthermore, CCNB2, NUSAP1 and TK1 were highly correlated with the HCC grade. It was also indicated that the mRNA expression of CCNB2, NUSAPA and TK1 was increased in primary HCC tissues when compared with that in adjacent tissues. The present study identified that the CCNB2, NUSAP1 and TK1 genes may serve as prognostic markers for HCC, and may be of value from the perspectives of basic research and clinical treatment of HCC.
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PMID:CCNB2, NUSAP1 and TK1 are associated with the prognosis and progression of hepatocellular carcinoma, as revealed by co-expression analysis. 3225 49