HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Frequent inactivation of RUNX3 in endometrial carcinoma.

AbstractOBJECTIVE:
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.
AuthorsTatsuo Yoshizaki, Takayuki Enomoto, Masami Fujita, Yutaka Ueda, Takashi Miyatake, Kazuko Fujiwara, Takahito Miyake, Toshihiro Kimura, Kiyoshi Yoshino, Tadashi Kimura
JournalGynecologic oncology (Gynecol Oncol) Vol. 110 Issue 3 Pg. 439-44 (Sep 2008) ISSN: 1095-6859 [Electronic] United States
PMID18572225 (Publication Type: Journal Article)
Chemical References
  • Core Binding Factor Alpha 3 Subunit
  • RNA, Messenger
  • Runx3 protein, human
Topics
  • Cell Line, Tumor
  • Core Binding Factor Alpha 3 Subunit (biosynthesis, genetics)
  • DNA Methylation
  • Endometrial Neoplasms (genetics, metabolism, pathology)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Genes, Tumor Suppressor
  • Humans
  • Immunohistochemistry
  • Loss of Heterozygosity
  • RNA, Messenger (biosynthesis, genetics)
  • Reverse Transcriptase Polymerase Chain Reaction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: