BACKGROUND: The mechanisms of estrogen insensitivity or estrogen resistance in ovarian cancer cells are not known. Studies on regulation of the estrogen receptor (ER) gene have suggested a role for epigenetics in silencing ER expression. MATERIALS AND METHODS: Cells from insensitive ovarian cancer cells, SKOV3 and HEY, were cultured with and without the DNA methyltransferase (DNMT) inhibitor, 5-aza-2'-deoxycytidine (AzaC) and the histone deacetylase (HDAC) inhibitor, trichostatin (TSA). ERbeta promoter methylation was examined using bisulfite sequencing. RNA was collected for oligonucleotide array studies. RESULTS: Cell type-specific ERbeta promoter methylation was found as well as relative hypomethylation of the ERbeta promoter in SKOV3 compared to HEY cells. Preferential demethylation of specific CpGs by different treatments was found. AzaC and TSA resulted in significant tumor growth inhibition and alterations in expression of numerous genes. CONCLUSION: The ERbeta promoter is differentially methylated in ovarian cancer cells. Moreover, AzaC and TSA can inhibit ovarian cancer cell growth.
BACKGROUND: The mechanisms of estrogen insensitivity or estrogen resistance in ovarian cancer cells are not known. Studies on regulation of the estrogen receptor (ER) gene have suggested a role for epigenetics in silencing ER expression. MATERIALS AND METHODS: Cells from insensitive ovarian cancer cells, SKOV3 and HEY, were cultured with and without the DNA methyltransferase (DNMT) inhibitor, 5-aza-2'-deoxycytidine (AzaC) and the histone deacetylase (HDAC) inhibitor, trichostatin (TSA). ERbeta promoter methylation was examined using bisulfite sequencing. RNA was collected for oligonucleotide array studies. RESULTS: Cell type-specific ERbeta promoter methylation was found as well as relative hypomethylation of the ERbeta promoter in SKOV3 compared to HEY cells. Preferential demethylation of specific CpGs by different treatments was found. AzaC and TSA resulted in significant tumor growth inhibition and alterations in expression of numerous genes. CONCLUSION: The ERbeta promoter is differentially methylated in ovarian cancer cells. Moreover, AzaC and TSA can inhibit ovarian cancer cell growth.
Authors: X Yang; A T Ferguson; S J Nass; D L Phillips; K A Butash; S M Wang; J G Herman; N E Davidson Journal: Cancer Res Date: 2000-12-15 Impact factor: 12.701
Authors: Ahmedin Jemal; Rebecca Siegel; Elizabeth Ward; Taylor Murray; Jiaquan Xu; Michael J Thun Journal: CA Cancer J Clin Date: 2007 Jan-Feb Impact factor: 508.702
Authors: P Pujol; J M Rey; P Nirde; P Roger; M Gastaldi; F Laffargue; H Rochefort; T Maudelonde Journal: Cancer Res Date: 1998-12-01 Impact factor: 12.701
Authors: Susan H Wei; Chuan-Mu Chen; Gordon Strathdee; Jaturon Harnsomburana; Chi-Ren Shyu; Farahnaz Rahmatpanah; Huidong Shi; Shu-Wing Ng; Pearlly S Yan; Kenneth P Nephew; Robert Brown; Tim Hui-Ming Huang Journal: Clin Cancer Res Date: 2002-07 Impact factor: 12.531
Authors: James V Lacey; Pamela J Mink; Jay H Lubin; Mark E Sherman; Rebecca Troisi; Patricia Hartge; Arthur Schatzkin; Catherine Schairer Journal: JAMA Date: 2002-07-17 Impact factor: 56.272
Authors: Verena Kirn; Rong Shi; Sabine Heublein; Julia Knabl; Margit Guenthner-Biller; Ulrich Andergassen; Claudius Fridrich; Wolfram Malter; Jan Harder; Klaus Friese; Doris Mayr; Udo Jeschke Journal: J Cancer Res Clin Oncol Date: 2014-06-08 Impact factor: 4.553
Authors: Kinga Tóth; Orsolya Galamb; Sándor Spisák; Barnabás Wichmann; Ferenc Sipos; Gábor Valcz; Katalin Leiszter; Béla Molnár; Zsolt Tulassay Journal: Pathol Oncol Res Date: 2011-01-26 Impact factor: 3.201
Authors: Gloria S Huang; Marc J Gunter; Rebecca C Arend; Maomi Li; Hugo Arias-Pulido; Eric R Prossnitz; Gary L Goldberg; Harriet O Smith Journal: Am J Obstet Gynecol Date: 2010-06-03 Impact factor: 8.661
Authors: Francesmary Modugno; Robin Laskey; Ashlee L Smith; Courtney L Andersen; Paul Haluska; Steffi Oesterreich Journal: Endocr Relat Cancer Date: 2012-11-09 Impact factor: 5.678