RRC ID 43398
Author Yoshizaki T, Enomoto T, Fujita M, Ueda Y, Miyatake T, Fujiwara K, Miyake T, Kimura T, Yoshino K, Kimura T.
Title Frequent inactivation of RUNX3 in endometrial carcinoma.
Journal Gynecol. Oncol.
Abstract OBJECTIVE:Our objective was to determine whether RUNX3 tumor suppressor is inactivated in endometrial carcinoma.
METHODS:We have investigated 24 endometrial carcinomas, 3 endometrial carcinoma cell lines, and 9 normal endometria for genetic and epigenetic alterations of RUNX3. Reverse-transcription PCR (RT-PCR), methylation-specific PCR (MS-PCR) analysis, and loss of heterozygosity (LOH) analysis were performed. We also tested RUNX3 protein expression by immunohistochemistry.
RESULTS:Using RT-PCR technique, we observed a significant loss of RUNX3 mRNA expression in nine of 24 endometrial carcinomas (38%) and in all 3-cell lines (100%). In contrast, all nine of the normal endometria showed an abundant expression of RUNX3 mRNA. Methylation-specific PCR (MS-PCR) analysis of the CpG islands of RUNX3 showed the promoter region to be hypermethylated in 18 of 21 analyzed carcinomas (86%), whereas only two of nine normal endometria (22%) were methylated (p<0.01). By using two polymorphic microsatellite markers, D1S199 and D1S1676, we detected 1p36 LOH in 7 of 21 carcinomas (33%). We observed a significant relationship between the loss of RUNX3 mRNA expression and this regional LOH (p<0.01). Immunohistochemical staining showed that RUNX3 protein expression was lost in 12 of 21 endometrial carcinomas (57%). We observed a significantly more frequent loss of RUNX3 protein expression in the histologically higher-grade tumors (Grade 3) than in Grade 1 or 2 tumors (p<0.01).
CONCLUSION:These findings indicate that RUNX3 inactivation may play an important role in carcinogenesis of the endometrium, especially in high-grade endometrial carcinoma.
Volume 110(3)
Pages 439-44
Published 2008-9
DOI 10.1016/j.ygyno.2008.05.004
PII S0090-8258(08)00358-2
PMID 18572225
MeSH Cell Line, Tumor Core Binding Factor Alpha 3 Subunit / biosynthesis Core Binding Factor Alpha 3 Subunit / genetics* DNA Methylation Endometrial Neoplasms / genetics* Endometrial Neoplasms / metabolism Endometrial Neoplasms / pathology Female Gene Expression Regulation, Neoplastic Gene Silencing Genes, Tumor Suppressor Humans Immunohistochemistry Loss of Heterozygosity RNA, Messenger / biosynthesis RNA, Messenger / genetics Reverse Transcriptase Polymerase Chain Reaction
IF 4.393
Times Cited 11
Human and Animal Cells