Analysis of the methylation status of the SFRP genes in ovarian clear cell carcinoma

• Main Authors: Li-Hsin Su, 蘇立欣
• Other Authors: 張淑芬
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/73791113880304690055

碩士 === 臺北醫學大學 === 醫學科學研究所 === 97 === Tumor suppressor genes are known to be inactivated by epigenetic modifications including promoter methylation. Secreted frizzled-related proteins (SFRPs) are extracellular signaling molecules that antagonize the Wnt signaling pathway. Ovarian clear cell carcinoma constitutes 12% of surface epithelial ovarian cancer in Taiwan. However, the role of SFRP genes in ovarian clear cell carcinoma molecular mechanism remains unknown. We investigated the SFRP1 and SFRP5 promoter status and demonstrated that SFRP5 gene promoter was methylated in 42% (5/12) ovarian clear cell carcinoma tissues and in 100% (5/5) ovarian clear cell carcinoma cell lines, compared with 0% (0/15) benign ovarian cyst and 20% (3/15) serous ovarian carcinoma tissues. And the SFRP1 gene promoter methylated only in 40% (2/5) ovarian clear cell carcinoma cell lines. Our results show that endogenous SFRP5 mRNA expression can be detected in four (80%) of the five ovarian clear cell carcinoma cell lines and is higher than that detected in normal lymphocytes. Treatment with the demethylating agent 5-aza-2''- deoxycytidine for 15 days rescued SFRP5 mRNA expression (60%, 3/5). Endogeous SFRP1 mRNA expression is absent in two (40%) of the five ovarian clear cell carcinoma cell lines. But treatment with the demethylating agent did not rescue SFRP1 mRNA expression nor restore SFRP1 promoter methylation atatus. We also find that suppressed ovarian cell carcinoma cell growth and migration ability.