Transcriptional Suppression DNA Methylation and Histone Deacetylation of the Regulator of G Protein Signaling 10 RGS10 Gene in Ovarian Cancer Cells
Yazarlar (9)
University Of Georgia, Amerika Birleşik Devletleri
Prof. Dr. Ercan ÇAÇAN
Georgia State University, Amerika Birleşik Devletleri
College Of Medicine, Amerika Birleşik Devletleri
College Of Medicine, Amerika Birleşik Devletleri
College Of Medicine, Amerika Birleşik Devletleri
University Of Georgia, Amerika Birleşik Devletleri
University Of Georgia, Amerika Birleşik Devletleri
Georgia State University, Amerika Birleşik Devletleri
University Of Georgia, Amerika Birleşik Devletleri
| Makale Türü |
Özgün Makale
|
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Plos One |
| Dergi ISSN | 1932-6203 Wos Dergi Scopus Dergi |
| Dergi Tarandığı Indeksler | SCI-Expanded |
| Dergi Grubu | Q4 |
| Makale Dili | İngilizce |
| Basım Tarihi | 03-2013 |
| Cilt No | 8 |
| Sayı | 3 |
| Sayfalar | 60185 / 0 |
| DOI Numarası | 10.1371/journal.pone.0060185 |
| Makale Linki | http://dx.plos.org/10.1371/journal.pone.0060185 |
| Özet |
| RGS10 regulates ovarian cancer cell growth and survival, and RGS10 expression is suppressed in cell models of ovarian cancer chemoresistance. However, the mechanisms governing RGS10 expression in ovarian cancer are poorly understood. Here we report RGS10 suppression in primary ovarian cancer and CAOV-3 ovarian cancer cells compared to immortalized ovarian surface epithelial (IOSE) cells, and in A2780-AD chemoresistant cells compared to parental A2780 cells. RGS10-1 and RGS10-2 transcripts are expressed in ovarian cancer cells, but only RGS10-1 is suppressed in A2780-AD and CAOV-3 cells, and the RGS10-1 promoter is uniquely enriched in CpG dinucleotides. Pharmacological inhibition of DNA methyl-transferases (DNMTs) increased RGS10 expression, suggesting potential regulation by DNA methylation. Bisulfite sequencing analysis identified a region of the RGS10-1 promoter with significantly enhanced DNA methylation in chemoresistant A2780-AD cells relative to parental A2780 cells. DNA methylation in CAOV-3 and IOSE cells was similar to A2780 cells. More marked differences were observed in histone acetylation of the RGS10-1 promoter. Acetylated histone H3 associated with the RGS10-1 promoter was significantly lower in A2780-AD cells compared to parental cells, with a corresponding increase in histone deacetylase (HDAC) enzyme association. Similarly, acetylated histone levels at the RGS10-1 promoter were markedly lower in CAOV-3 cells compared to IOSE cells, and HDAC1 binding was doubled in CAOV-3 cells. Finally, we show that pharmacological inhibition of DNMT or HDAC enzymes in chemoresistant A2780-AD cells increases RGS10 expression and enhances cisplatin toxicity. These data suggest that histone de-acetylation and DNA methylation correlate with RGS10 suppression and chemoresistance in ovarian cancer. Markers for loss of RGS10 expression may identify cancer cells with unique response to therapeutics. © 2013 Ali et al. |
| Anahtar Kelimeler |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| WoS | 42 |
| SCOPUS | 45 |
| Google Scholar | 59 |