Inactivation of ADAMTS18 by aberrant promoter hypermethylation contribute to lung cancer progression

Our results demonstrated that the tumor suppressor gene ADAMTS18 was downregulated in lung cancer by promoter CpG methylation, and it promoted sensitivity to cisplatin via epidermal growth factor receptor/protein kinase B signaling. Our study suggests that ADAMTS18 promoter methylation is a potential epigenetic biomarker for early detection of lung cancer and warrants investigation as therapeutic target for early ‐stage lung cancer. AbstractLung cancer is the most frequently diagnosed cancer worldwide. Epigenetic regulation contributes to lung cancer pathogenesis. TheADAMTS18 tumor suppressor gene is inactivated in some cancers, but its involvement in lung cancer has not been shown. Immunohistochemistry, quantitative reverse ‐transcription polymerase chain reaction (qRT‐PCR), and methylation‐specific PCR were used to assay ADAMTS18 expression and promoter methylation in lung tumor tissues and adjacent tissues. Cell viability, transwell, and wound‐healing assays, as well as flow cytometry were used to characteri ze the biological activity of ADAMTS18. The influence of ADAMTS18 on protein expression was assayed using western blots analysis, and its effect on chemosensitivity was assayed by the response to cisplatin. We found thatADAMTS18 was silenced in lung cancer cells by promoter methylation. Demethylation by the DNA methyltransferase inhibitor 5 ‐aza‐2′‐deoxycytidine, with or without the histone deacetylase inhibitor trichostatin A, restoredADAMTS18 expre...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research