RUNX3 gene methylation in epithelial ovarian cancer tissues and ovarian cancer cell lines.
Methylation plays an important role in the regulation of gene expression in many cancer tissues. RUNX3 is an important tumor suppressor gene located on human chromosome 1p36.1, and many tumors do not express it due to methylation of the promoter region of the CpG island. The molecular mechanisms involved in RUNX3 gene expression and epithelial ovarian cancer are not fully understood. This study investigates the relationship between RUNX3 methylation and expression in ovarian cancer. The methylation of the RUNX3 gene promoter region was measured in 32 primary epithelial ovarian cancer samples and corresponding nonmalignant ovarian tissues, 36 benign epithelial ovarian tumor tissues, and 10 normal ovarian tissues by methylation-specific PCR (MSP) and RT-PCR. The relationships between RUNX3 methylation status, expression, and clinicopathologic characteristics were analyzed. RUNX3 methylation was further assessed by MSP and RT-PCR before and after 5-aza-2'-deoxycytidine (5-aza-dc) treatment in normal and cancer cell lines. We detected RUNX3 methylation in 53.1% of primary ovarian cancer tumors, 16.7% of benign ovarian tumors, and 28% of nonmalignant tissues surrounding ovarian cancers. No methylation was detected in normal ovarian tissues. No significant correlation between RUNX3 methylation and clinicopathological characteristics was observed. The RT-PCR results found RUNX3 expression in all normal ovarian tissues (10/10) and in most of the unmethylated ovarian cancer tissues (12/15); in contrast, it was not detected in most of the RUNX3-methylated ovarian cancer tissues (16/17). Our data suggest that methylation plays a critical role in the regulation of RUNX3 repression, and that it is significantly correlated with RUNX3 mRNA expression in ovarian cancer tissues (p = 0.006).
Zhang
Shiqian
S
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Shandong Province, People's Republic of China. r370112@126.com
Wei
Lingxia
L
Zhang
Aifeng
A
Zhang
Linlin
L
Yu
Hao
H
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
D050677:Core Binding Factor Alpha 3 Subunit; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C493729:Runx3 protein, human; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine