Aberrant methylation accounts for cell adhesion-related gene silencing during @entity5954 and @entity107 induced multistep @entity35 lung XXXX associated with overexpression of @entity54389 .

@entity108 @entity54389 @entity14923 @entity5 @entity17937 @entity107 @entity71960 @entity17935 @entity54390 @entity35 @entity5954 @entity9623 @entity105 @entity11019 @entity11508
To evaluate the significance of alterations in cell adhesion-related genes methylation during lung multistep @entity105 induced by the genotoxic carcinogens @entity5954 ( @entity9623 ) and @entity107 ( @entity108 ), tissue samples microdissected from @entity9623 / @entity108 -induced @entity35 lung @entity105 model were subjected to methylation-specific PCR to evaluate the DNA methylation status of @entity71960 , @entity11019 , @entity17937 and @entity17935 . Immunohistochemistry was used to determine protein expression of @entity71960 , @entity11019 , @entity17935 and the DNA methyltransferases (DNMTs) 1, 3a and 3b. @entity17937 hypermethylation was not detected in any tissue. @entity71960 , @entity11019 and @entity17935 hypermethylation was correlated with the loss of their protein expression during the progression of pathologic lesions. The prevalence of DNA methylation of at least one gene and the average number of methylated genes increased with the histological progression. @entity14923 and @entity54389 protein expression increased progressively during the stages of lung @entity105 , whereas @entity54390 overexpression was only found in several samples. Furthermore, @entity14923 protein expression levels were correlated with @entity71960 methylation, and @entity54389 protein expression levels were correlated with @entity71960 , @entity11019 and @entity17935 methylation. The average number of methylated genes during @entity105 was significantly correlated with @entity14923 and @entity54389 protein expression levels. Moreover, mRNA expression of @entity71960 significantly increased after treatment with DNMT inhibitor @entity11508 in @entity71960 -methylated @entity5 cell lines. Our findings suggest that an accumulation of hypermethylation accounts for cell adhesion-related gene silencing is associated with dynamic changes in the progression of @entity9623 / @entity108 -induced @entity35 lung @entity105 . We suggest that @entity14923 and @entity54389 protein overexpression may be responsible for this aberrant DNA methylation.
