Abstract
AKAP12 play an important role in tumor growth suppression by inducing apoptosis with the regulation of multiple molecules in the cell cycle progression. This function of AKAP12 gene might be inhibited by epigenetic repression like other tumor suppressor genes. In the previous report, we showed that AKAP12 inactivation was associated with the promoter methylation in the lung cancer. In the present study, to investigate whether the promoter methylation of AKAP12 gene affects the expression of AKAP12 protein, we carried out in vitro methylation assay and protein analysis. We also performed methylation profiling of AKAP12 promoter using the bisulfite‐sequencing in the additional matched normal and lung cancer tissue DNA, and serum DNA samples. The expression of the AKAP12 protein was down‐regulated in lung cancer cells. The reduced expression of AKAP12 protein was restored by the treatment of the DNA methyltransferase inhibitor. AKAP12 fragments pGL3‐837 M (methylated) and pGL3‐443 M (methylated) showed low luciferase activities compared to the unmethylated constructs. CpG islands of the AKAP12 promoter were frequently methylated in tumor samples compared with normal tissue samples. Furthermore, CpG islands methylation of AKAP12 was more frequently found in non‐relapse patients after surgery compared to early relapse patients within 2 years after surgery.
In conclusion, our results demonstrated that AKAP12 expression was regulated by DNA methylation and AKAP12 promoter methylation was associated with lung cancer development and prognosis after surgery. This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A010250) and Seoul Research and Business Development Program (10574)
Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C24.
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