Then performed a microarray analysis of Changes in gene expression between the control and 8 h Gleevec treated cells to examine. We first compared with K562 cells untreated HL60 untreated cells and analyzed more comparison Panobinostat between K562 cells with Gleevec K562 cells is treated and embroidered. Our microarray analysis, we observed different patterns of supply Changes in gene expression in both S Protect comparisons. Are embroidered in K562 cells, and compared with the HL60 cells to a total of 855 and 2182 genes significantly upregulated and downregulated. Comparing K562 cells were treated with Gleevec, compared K562 cells and embroidered to 1114 genes were upregulated and 113 observed significantly downregulated. overlapping genes are additives tzlichen file 1 listed.
We then tried to identify control groups of genes were compared in K562 K562 Gleevec treated group enriched group. This was confirmed by the comparison of our data table against the curator known gene reached sets are CX-4945 available from the database of molecular signatures. In line with our results, Western, our analysis revealed that the genes play a series of repressed genes in K562 cells together Gleevectreated were within the JAK / STAT signaling pathway grouped. Three genes have been Selected from 1B Hlt and then validated using real-time PCR. One in particular, providing a down-regulation PIK3CG, a gene that the catalytic component of the phosphoinositide 3-kinase, non-tyrosine kinase receptor.
A significant difference in the downregulation of nearly three-fold was observed when K562 cells were treated with Gleevec against K562 cells and embroidered treated therewith. Although we have not observed significant down-regulation of hTERT mRNA in microarray analysis, real-time PCR results showed a significant down-regulation of hTERT mRNA in K562 cells treated Gleevec. The conflicting results hTERT gene expression can be described by the reduction of the sensitivity of the variation in gene expression with respect to the microarray real-time PCR. But we found many genes that are used in gene-enriched telomere, Verl EXTENSIONS involved of telomeres and telomeric ends of the package were regulated. As n Chstes we found that Gleevec can inhibit hTERT expression at the protein level in treated K562 cells with 1 M Gleevec at different times.
Surprisingly, there was no significant change in the H see the expression of the protein of 16 h treatment hTERT Gleevec. This k Nnte be a short half-life of hTERT mRNA to the long half-life of hTERT protein in K562 cells, which then causes a correlation between protein and the level of indirect transcriptional compared. We agrees on the treatment after 24 h leased Gleevec, And we see no significant Change in the H Expression of hTERT protein at 24 and 36 h was observed. There is a slight decrease in the level of hTERT protein in 48 h, suggesting that Gleevec has no significant influence on the reduction of the rate of degradation of hTERT in the short-term treatment. We also observed and best CONFIRMS in Figure 2c, the activity that Gleevec t reduces the BCR-ABL tyrosine kinase by the abolition of the phosphorylation of BCR-ABL and thus eliminates the phosphorylation of STAT5. STAT5 is activated by BCR-ABL and is involved in the pathogenesis of CML. To function as a transcriptional activator STAT5 well known and has been shown to be