1. Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
2. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
3. Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
4. Department of Pathology, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Republic of Korea
5. Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Republic of Korea
*These authors have contributed equally to this work.
A better understanding of tumor biology is important in the identification of molecules that are downregulated in malignancy and in determining their role in tumor suppression. B-cell translocation gene 1 (BTG1) has been shown to act as a tumor suppressor in several types of human malignancy. In this study, we analyzed BTG1 expression in ovarian carcinoma cell lines, and we investigated the mechanism underlying the observed alterations. The methylation status of the BTG1 promoter region was determined by methylation-specific polymerase chain reaction, and the effect of demethylation on BTG1 expression was analyzed. BTG1 protein expression in ovarian high-grade serous carcinoma tissue samples was evaluated using immunohistochemistry. BTG1 mRNA and protein expression were reduced in ovarian carcinoma cells. In BTG1-silenced ovarian cancer cells, the BTG1 promoter was highly methylated. Treatment with 5-aza-deoxycytidine significantly elevated BTG1 mRNA and protein expression. Immunostaining demonstrated that BTG1 expression was significantly lower in ovarian carcinoma tissue samples than nonpathological ovaries and fallopian tubes. We demonstrated that BTG1 silencing in ovarian carcinoma occurs through epigenetic repression and is involved in the ovarian carcinogenesis. Our data suggest that BTG1 is a potential therapeutic target for patients with ovarian carcinoma.
Keywords: ovary, ovarian carcinoma, B-cell translocation gene 1, downregulation, promoter hypermethylation