title: The role of the tumor suppressor RUNX3 in giant cell tumor of the bone.
abstract: RUNX3 is a tumor suppressor gene localized in 1p36. In various human tumors,             the region is frequently inactivated through hypermethylation, histone modulation             and other processes. Recent studies have suggested that loss of RUNX3 expression             is involved in stomach, colon and breast cancer. However, the relationship between             RUNX3 expression and giant cell tumor of the bone (GCTB) remains elusive. The             aim of our study was to elucidate the roles of RUNX3 expression in carcinogenesis             and progression of giant cell tumor of the bone. The levels of RUNX3 mRNA and             protein were evaluated in human GCTB specimens and cell lines. To assess RUNX3             methylation we employed methylation-specific polymerase chain reaction using GCTB             specimens and cell lines. In addition, to examine the roles of RUNX3 in giant             cell tumor of the bone, GCTB cells were transfected with pcDNA3.1-RUNX3 (RUNX3             was cloned into the pcDNA3.1 plasmid). Flow cytometry (FCM) was used to analyze             the apoptosis and cell cycle. The mobility of cells was tested by transwell migration             assay. The expression rates of RUNX3 in patients with GCTB were significanly lower             than normal bone tissues. Thirty of 47 human cancer specimens exhibited suppression             (P<0.05). Down-regulation of RUNX3 mRNA in the same GCTB cell lines was associated             with RUNX3 DNA methylation. In in vitro experiments, exogenous expression of RUNX3             strongly inhibited cell growth in GCTB by MTT (P<0.05), induced apoptosis as             evidenced by Annexin V-FITC and increased G1 phase ratio by PI (P<0.05). Transwell             migration assay showed that less RUNX3 positive cells migrated to the lower side             of the membrane than negative ones (P<0.05). These results show that RUNX3             is a tumor suppressor in GCTB. RUNX3 DNA methylation may be the molecular basis             for its lower expression. These data may be applied in GCTB for diagnostics and             therapeutics.
authors.affiliation: Department of Orthopaedics, China Medical University, Shenyang, People's Republic of China.
authors.forename: Ya-Xin
authors.initials: YX
authors.lastname: Han
authors.forename: De-Yong
authors.initials: DY
authors.lastname: Liang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D019175:DNA Methylation; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D018212:Giant Cell Tumor of Bone / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009367:Neoplasm Staging / Q000379:methods; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection / Q000379:methods
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D012333:RNA, Messenger; C493729:Runx3 protein, human