G1 cells beyond the point on embroidered. LY2603618 IC-83 In the class, appears melanomas with a mutant allele B RAF effective G1 checkpoint With the IR. However, these lines appear significantly attenuated Cht G2 checkpoint function, dodge with an average of 38 cells G2 checkpoint It. Class of melanoma with a mutated allele N RAS posted an average of 21 cells escape G2 checkpoint It D Damping moderate, but insignificant compared to MHN. This class of melanoma also showed G1 checkpoint response variable that is not significant from MHN. Defects in cell cycle checkpoint function were relatively h Frequently in melanoma cell lines, the hypothesis that genetic instability to in melanoma can be d partly to defects in the system in response to DNA-Sch the. Defects in the checkpoint function seems ZUF not Sort llig among melanoma lines.
For example, the four melanoma lines with wild-type N-RAS and B alleles of the RAF and efficient DNA damage checkpoint function G2 BSI-201 all displayed defective DNA-Sch The checkpoint G1 function. These results suggest that M ngel In the G1 and G2 checkpoints In melanomas of different genetic Ver Changes Arise. Thus, there are at least two fa Ons whose function DNA Sch Ending Checkpoint can through the development of melanoma, the inactivation of the affected control point G1 independent Ngig B and N RAF RAS mutations and D Damping control G2 RAF mutations associated with B function signatures DNA damage checkpoint defective after the occurrence of changes Funktionsst Into the checkpoints established Cycle sch interred The DNA of cells in melanoma lines, the global gene expression was assessed research signatures that have been with St Changes brought together.
The microarray Agilent 44K oligonucleotide was used for human expression profiling, and each cell line was analyzed once. We have already reported that Melanoma lines with wild-type alleles RAS RAF black and a unique signature of gene expression relative to the display lines with mutations in the RAS and RAF NB. The oncogenic mutations with high phospho ERK 1 2 brought together and obtained Hte expression of ERK1 100 2 mRNA sensitive. The statistical analysis of microarray data sets also identified genes that were functional activity T stations on DNA Sch Joined the embroidery. Two Ans PageSever tested genes between strains St Melanoma lines and NHM function of the efficiency function embroidered on vary.
Significance analysis of microarrays was often applied to identify data microarray on genes that are correlated with certain treatments or cell types. A new method for Bayesian statistical theory was developed. Checkpoint function as Re variable have been analyzed in order to compare the answers to lines checkpoints Most and less than the median response with quantitative data. For the analysis of the function of the control points G1 in melanocytes and melanoma cells, identified SAT 26 genes that were significantly different in the two classes 0,1, w While the Bayesian analysis identified 166 different genes that were significant. Genes that are on both lists well-established p53 target genes CDKN1A and DDB2 that were ert at lower levels in melanoma checkpoint ge U G1 defective. Cell proliferation associated genes Several ide