Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 주웅 | * |
dc.contributor.author | 안정혁 | * |
dc.contributor.author | 성혜윤 | * |
dc.date.accessioned | 2018-12-07T16:30:34Z | - |
dc.date.available | 2018-12-07T16:30:34Z | - |
dc.date.issued | 2017 | * |
dc.identifier.issn | 2092-6413 | * |
dc.identifier.other | OAK-20903 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/247353 | - |
dc.description.abstract | Metastasis is a major cause of therapeutic failure in ovarian cancer. To elucidate molecular mechanisms of ovarian cancer metastasis, we previously established a metastatic xenograft mouse model using human ovarian carcinoma SK-OV-3 cells. Using gene expression profiling, we found that γ-aminobutyric acid (GABA)A receptor π subunit (GABRP) expression was upregulated (>4-fold) in metastatic tissues from our xenograft mice compared with SK-OV-3 cells. Importantly, GABRP knockdown diminished the migration and invasion of SK-OV-3 cells, and reduced extracellular signal-regulated kinase (ERK) activation while overexpression of GABRP exhibited significantly increased cell migration, invasion and ERK activation. Moreover, treatment with the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor U0126 similarly suppressed the migration and invasion of SK-OV-3 cells, implying that GABRP promotes these cellular behaviors by activating the MAPK/ERK pathway. Using genome-wide DNA methylation profiling, we identified hypomethylated CpG sites in the GABRP promoter in metastatic tissues from the xenograft mice compared with SK-OV-3 cells. Treatment with a DNA methyltransferase inhibitor demonstrated that methylation at -963 bp from the GABRP transcription start site (-963 CpG site) was critical for the epigenetic regulation of GABRP. Finally, we analyzed human ovarian cancer patient samples and showed DNA hypomethylation at the GABRP -963 CpG site in advanced stage, but not early-stage, primary tumors compared with their paired normal tissues. These findings suggest that GABRP enhances the aggressive phenotype of ovarian cancer cells, and that the DNA methylation status of the GABRP -963 CpG site may be useful for predicting the metastatic potential in ovarian cancer patients. | * |
dc.language | English | * |
dc.title | Aberrant epigenetic regulation of GABRP associates with aggressive phenotype of ovarian cancer | * |
dc.type | Article | * |
dc.relation.issue | 5 | * |
dc.relation.volume | 49 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.index | KCI | * |
dc.relation.startpage | e335 | * |
dc.relation.journaltitle | Experimental & molecular medicine | * |
dc.identifier.doi | 10.1038/emm.2017.62 | * |
dc.identifier.wosid | WOS:000404159600009 | * |
dc.identifier.scopusid | 2-s2.0-85042463316 | * |
dc.author.google | Sung H.Y. | * |
dc.author.google | Yang S.-D. | * |
dc.author.google | Ju W. | * |
dc.author.google | Ahn J.-H. | * |
dc.contributor.scopusid | 주웅(8873659700) | * |
dc.contributor.scopusid | 안정혁(35081632000) | * |
dc.contributor.scopusid | 성혜윤(57197173696) | * |
dc.date.modifydate | 20240130120134 | * |