Premium
Transcriptional suppression, DNA methylation, and histone deacetylation of the Regulator of G‐protein Signaling 10 (RGS10) gene in ovarian cancer cells
Author(s) -
Ali Mourad Wagdy,
Cacan Ercan,
Liu Yuying,
Eblen Scott T.,
Greer Susanna F.,
Hooks Shelley B.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1095.1
Subject(s) - ovarian cancer , epigenetics , dna methylation , cancer research , biology , acetylation , cell growth , histone , cancer cell , cancer epigenetics , akt2 , cancer , signal transduction , microbiology and biotechnology , gene expression , gene , histone methyltransferase , genetics , akt1 , pi3k/akt/mtor pathway
Regulators of G‐Protein Signaling (RGS) Proteins suppress GPCR‐mediated growth and survival signaling in multiple cancers. We have shown that RGS10 is downregulated in ovarian cancer chemoresistance, and RGS10 expression levels alter ovarian cancer cell growth and sensitivity to cytotoxic drugs. This suggests that the suppression of RGS10 may contribute to ovarian cancer progression and the development of chemoresistance by indirectly amplifying GPCR‐mediated growth and survival signaling. The current study investigates the epigenetic regulation of RGS10 expression in ovarian cancer. RGS10 expression was reduced in clinical ovarian cancer and CAOV‐3 ovarian cancer cells compared to control immortalized ovarian surface epithelial (IOSE) cells. Histone acetylation at RGS10 promoters was decreased in CAOV‐3 compared to IOSE cells, with a corresponding increase in HDAC1 association. Similar loss of histone acetylation and increased HDAC1 binding was observed in chemoresistant versus chemosensitive ovarian cancer cells. Further, enhanced DNA methylation was observed in RGS10 promoter of chemoresistant cells. Our results suggest that epigenetic modifications correlate with the loss of RGS10 expression in ovarian cancer cells, and may contribute to the amplification of GPCR‐mediated growth and survival signaling. This research is funded by NIH and the Marsha Rivkin Center.