Abstract 4618: Effect of restoration of estrogen receptor-α (ER α) expression on drug sensitivities of gastric cancer cell lines

Abstract

Abstract Introduction: The significance of expression of estrogen receptor-α (ER α) and hormone manipulation is not established in gastric cancer. Positivity of ER α expression in gastric cancer ranges from 0-67%. We previously reported that promoter methylation of ER α is associated with loss of ER α in gastric cancer cell lines. The aim of this study was to examine the changes in sensitivity to tamoxifen and 5-fluorouracil (5-FU) after induction of ER α by the DNA methyltransferase-1(DNMT1) inhibitor 5′-aza-deoxycytidine (AZA) and the histone deacetylase (HDAC) inhibitor trichostatin A (TSA), following gene transfection of ER α into gastric cancer cell lines. Methods: ER α-negative gastric cancer cell lines including SNU-484, −638, and −71 were treated with AZA (10 μmol/L) and TSA (500 nmol/L). An ER α-encoding plasmid was transfected into an ER α-negative breast cancer cell line, MDA-MB-231, and gastric cancer cell lines. Cell proliferation was assayed in ER α-negative and -restored cell lines treated with tamoxifen (0, 1, 2.5, 5, 10, 15, 20, and 25 μM) or 5-FU (0, 0.02, 0.2, 2, 20, 200, and 1,000 μM). Results: Restoration of ER α expression in ER α-negative gastric cancer cell lines after treatment with AZA and TSA was confirmed by RT-PCR. Growth inhibition was more prominent in gastric cancer cell lines transfected with the ER α gene (with tamoxifen at a concentration of more than 15 μM) or treated with trichostatin (with tamoxifen at a concentration of more than 20 μM) than in ER α-negative gastric cancer cell lines. No differences in sensitivity to 5-FU were observed regardless of whether ER α was present or absent. Conclusion: The DNMT inhibitor AZA and the HDAC inhibitor TSA, together with tamoxifen, deserve further investigation as new targeted therapies in ER α-negative gastric cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4618.