Abstract P3-04-16: Estrogen receptor β agonists reduce breast cancer tumor growth in syngeneic mouse models

Abstract

Abstract The estrogen receptors (ER) play a significant role in breast cancer, with the majority of breast cancers expressing estrogen receptor alpha (ERα) and depending on its signaling. ERα has proliferative function, however, estrogen receptor beta (ERβ) has anti-proliferative functions. Recently, several selective ERβ agonists have been identified. The objective of this study was to determine the effectiveness of ERβ agonists in inhibiting the growth of distinct breast cancer cells both in-vitro and in-vivo, and to determine the mechanisms involved. The mouse mammary tumor cell lines, D2A1 and MM51, express both ERα and ERβ. Specifically D2A1 cells are dependent on estrogen for growth and have increased expression of aromatase. Additionally, D2A1 cells are very aggressive and highly metastatic; representing a good model of breast cancer progression. MM51 cells are Her2/neu positive and are an adequate model to study the crosstalk between growth factors and ER signaling. Syngeneic mouse tumor models were used to incorporate an intact immune system which plays a role in the tumor’s microenvironment. Our in-vitro studies demonstrate that ERβ agonists significantly inhibit cell growth in a dose dependent manner. Our syngeneic studies show that, in-vivo, ERβ agonists effectively reduce tumor volume and inhibit tumor progression. This study reveals that in addition to acting on ERβ, these agonists reduce the expression of ERα at both the mRNA and protein level, therefore modulating the ratio of ERα to ERβ. Additionally, treatment with ERβ agonists results in increases apoptosis through increased p53 expression, and cell cycle arrest through p27 and cyclin D1. Together, these studies demonstrate the therapeutic potential of ERβ agonists for the treatment of breast cancer. Citation Format: Cathy Samayoa, Naveen K Krishnegowda, Ratna K Vadlamudi, Rajeshwar R Tekmal. Estrogen receptor β agonists reduce breast cancer tumor growth in syngeneic mouse models [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-16.