Epigenetic regulation of RGS2 (Regulator of G-protein signaling 2) in chemoresistant ovarian cancer cells        
Yazarlar (1)
Prof. Dr. Ercan ÇAÇAN Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı Journal of Chemotherapy
Dergi ISSN 1120-009X Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI
Dergi Grubu Q4
Makale Dili İngilizce
Basım Tarihi 01-2017
Cilt No 29
Sayı 3
Sayfalar 173 / 178
DOI Numarası 10.1080/1120009X.2016.1277007
Makale Linki https://www.tandfonline.com/doi/full/10.1080/1120009X.2016.1277007
Özet
Regulator of G-protein signaling 2 (RGS2) is a GTPase-activating protein functioning as an inhibitor of G-protein coupled receptors (GPCRs). RGS2 dysregulation was implicated in solid tumour development and RGS2 downregulation has been reported in prostate and ovarian cancer progression. However, the molecular mechanism by which RGS2 expression is suppressed in ovarian cancer remains unknown. The expression and epigenetic regulation of RGS2 in chemosensitive and chemoresistant ovarian cancer cells were determined by qRT-PCR and chromatin immunoprecipitation assays, respectively. In the present study, the molecular mechanisms contributing to the loss of RGS2 expression were determined in ovarian cancer. The data indicated that suppression of RGS2 gene in chemoresistant ovarian cancer cells, in part, due to accumulation of histone deacetylases (HDACs) and DNA methyltransferase I (DNMT1) at the promoter region of RGS2. Inhibition of HDACs or DNMTs significantly increases RGS2 expression. These results suggest that epigenetic changes in histone modifications and DNA methylation may contribute to the loss of RGS2 expression in chemoresistant ovarian cancer cells. The results further suggest that class I HDACs and DNMT1 contribute to the suppression of RGS2 during acquired chemoresistance and support growing evidence that inhibition of HDACs/DNMTs represents novel therapeutic approaches to overcome ovarian cancer chemoresistance.
Anahtar Kelimeler
chemoresistance | DNA Methylation | histone acetylation | ovarian cancer | RGS2