Axin gene methylation status correlates with radiosensitivity of lung cancer cells

Abstract

BackgroundWe previously reported that Axin1 (Axin) is down-regulated in many cases of lung cancer, and X-ray irradiation increased Axin expression and inhibited lung cancer cells. The mechanisms, however, were not clear.MethodsFour lung cancer cell lines were used to detect the methylation status of Axin with or without X-ray treatment. Real-time PCR was used to quantify the expression of Axin, and western blot analysis was applied to measure protein levels of Axin, β-catenin, Cyclin D1, MMP-7, DNMTS, MeCP2 and acetylated histones. Flow cytometric analysis, colony formation assay, transwell assay and xenograft growth experiment were used to study the biological behavior of the cells with hypermethylated or unmethylated Axin gene after X-ray treatment.ResultsHypermethylated Axin gene was detected in 2 of 4 cell lines, and it correlated inversely with Axin expression. X-ray treatment significantly up-regulated Axin expression in H446 and H157 cells, which possess intrinsic hypermethylation of the Axin gene (P<0.01), but did not show up-regulation in LTE and H460 cells, which have unmethylated Axin gene. 2Gy X-ray significantly reduced colony formation (from 71% to 10.5%) in H157 cells, while the reduction was lower in LTE cells (from 71% to 20%). After X-ray irradiation, xenograft growth was significantly decreased in H157 cells (from 1.15 g to 0.28 g) in comparison with LTE cells (from 1.06 g to 0.65 g). Significantly decreased cell invasiveness and increased apoptosis were also observed in H157 cells treated with X-ray irradiation (P<0.01). Down-regulation of DNMTs and MeCP2 and up-regulation of acetylated histones could be detected in lung cancer cells.ConclusionsX-ray-induced inhibition of lung cancer cells may be mediated by enhanced expression of Axin via genomic DNA demethylation and histone acetylation. Lung cancer cells with a different methylation status of the Axin gene showed different radiosensitivity, suggesting that the methylation status of the Axin gene may be one important factor to predict radiosensitivity of the tumor.

Association between Dental Agenesis and Cancer-A Systematic Review of Literature

“…The AXIN2 gene may be the gene for dental agenesis that makes the connection to breast cancer. First, the AXIN2 gene has been mapped to chromosome 17q23-q24, which is a region that has a heterozygosity (LOH) in breast cancer [26]. Second, it was identified in high-grade breast tumors [26].…”

“…First, the AXIN2 gene has been mapped to chromosome 17q23-q24, which is a region that has a heterozygosity (LOH) in breast cancer [26]. Second, it was identified in high-grade breast tumors [26]. Third, it was found that the SNPs in AXIN2 were breast cancer.…”

Functional Profiling of Human MeCP2 by Automated Data Comparison Analysis and Computerized Expression Pathway Modeling

“…JUN and FOS also induce apoptotic cell death in cancer [ 20 ]. The MeCP2 protein is more highly expressed in most cancer tissues than in corresponding noncancerous tissues [ 21 ]. The up-regulation of apoptosis-related genes by MeCP2 RNA silencing suggests that the apoptosis-related genes might be suppressed in tumors with high MeCP2 expression.…”

“…The expression levels of six genes ( WDR42A, HNRNPA0, HIS1, RBM12, CYP7B1 and FOXC1 ) were decreased to below 25% of the control levels. Three genes ( HNRPA0, HIS1 , and FOXC1 ) have anti-apoptotic and proliferative functions [ 21 27 ].…”

Microrna-22 regulates smooth muscle cell differentiation from stem cells by targeting methyl cpg binding protein 2

“…X-ray-induced inhibition of lung cancer cells is mediated by enhanced expression of the Axin gene via genomic DNA demethylation and histone acetylation. Mechanically, it has been shown that MECP2 represses histone deacetylase, leading to transcriptional activation of the Axin gene via histone acetylation, thus suggesting a role for MECP2 in cancer prevention (Yang et al, 2013a, Esteller, 2005).…”