RASSF10 is epigenetically inactivated and induces apoptosis in lung cancer cell lines

Abstract Ras-association domain family 10 (RASSF10), the latest member of the RASSF family with Ras effector function, has been frequently inactivated by aberrant promoter hypermethylation in several human cancers. However, its role in lung cancer has remained unclear. In this study, we investigated the methylation status of RASSF10 by combined bisulfate restriction analysis (COBRA) and examined its preliminary function in lung cancer cell lines. RASSF10 was methylated in four out of six lung cancer cell lines, including NCI-H157, NCI-460, SPCA-1 and NCI-H446. Treatment with a DNA methylation inhibitor, 5-aza-2′-deoxycytiding (5-aza-DC), restored RASSF10 mRNA expression and the restoration of RASSF10 increased cell apoptosis in a dose dependent manner, whereas knockdown of RASSF10 improved cell proliferation ability and inhibited cell apoptosis rate significantly. Immunofluorescence revealed that RASSF10 protein was located in the cell membrane. Taken together, our data for the first time demonstrates the frequent epigenetic inactivation of RASSF10 in lung cancer cell lines. RASSF10 induces cell apoptosis and might function as a tumor suppressor gene in lung cancer.