Abstract LB-5: RUNX3 targets estrogen receptor α for proteasome-mediated degradation suppressing breast cancer tumorigenesis

Abstract

Abstract Transcription factor RUNX3 is inactivated in a number of malignancies including breast cancer and is suggested to function as a tumor suppressor. However, the exact mechanism for its tumor suppressor function in breast cancer remains elusive. Here we demonstrate that RUNX3 interacts with estrogen receptor α (ERα) and reduces ERα-mediated transactivation by stimulating the ubiquitination and proteasome-mediated degradation of ER. Consistent with its ability to reduce levels of ERα, expression of RUNX3 inhibits the estrogen-dependent proliferation and transformation potential of ER -positive MCF-7 breast cancer cells in liquid culture and in soft agar and suppresses the tumorigenicity of MCF-7 cells in mice. Thus, these studies reveal modulation of ERα stability as a novel mechanism by which RUNX3 functions as a tumor suppressor in ERα-positive breast cancer. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 LB-5.