title: Clinical importance and therapeutic implication of E-cadherin gene methylation in human ovarian cancer.
abstract: E-cadherin (E-cad) is widely expressed in epithelial cells and acts as a pivotal tumor suppressor. The promoter methylation of E-cad has been reported to closely relate to its downregulation in many kinds of cancers. E-cad expression and methylation status were detected by immunohistochemistry (IHC) and methylation-specific polymerase chain reaction (MS-PCR) in 50 ovarian cancer tissues. 5-Aza-2'-deoxycytidine (5-Aza-dC) was used to demethylate E-cad in SKOV3 and ES2 ovarian cancer cell lines, of which the effect was verified by Western blot and MS-PCR. Then MTT and transwell experiments were conducted to detect the capacity of cell proliferation and migration for these cells. Downregulation of E-cad expression was observed in 60 % of ovarian cancer tissues (30/50) by IHC, whereas MS-PCR result indicated that E-cad was methylated in 64 % of (32/50) ovarian cancer specimens. And E-cad expression was significantly correlated with E-cad methylation (P = 0.004). 5-Aza-dC was used to process SKOV3 and ES2 ovarian cancer cell lines. By MTT experiment, we found that the proliferation of 5-Aza-dC-treated SKOV3 and ES2 was significantly suppressed by 28.0 % (P < 0.05) and 32.3 % (P < 0.05). By transwell experiment, the motility of SKOV3 and ES2 was found to be significantly suppressed by 38.2 and 27.4 % (P < 0.05), respectively, after treated with 5-Aza-dC. E-cad methylation is one of the main reasons for the expression reduction in ovarian cancer. 5-Aza-dC treatment could significantly restore the expression of E-cad and suppress growth and invasion of SKOV3 and ES2 cells. These results suggest E-cad methylation may be a promising target for ovarian cancer therapy.
authors: Department of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, 515031, Guangdong, China, wuxiao@stu.edu.cn.
authors: Xiao
authors: X
authors: Wu
authors: Yi-xuan
authors: YX
authors: Zhuang
authors: Chao-qun
authors: CQ
authors: Hong
authors: Jiong-yu
authors: JY
authors: Chen
authors: Yan-jie
authors: YJ
authors: You
authors: Fan
authors: F
authors: Zhang
authors: Ping
authors: P
authors: Huang
authors: Ming-yao
authors: MY
authors: Wu
mesh_terms: D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D019175:DNA Methylation; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D055815:Young Adult
chemical_list: D015820:Cadherins; D004791:Enzyme Inhibitors; D000077209:Decitabine; D001374:Azacitidine