Abstract 2502: Role of TMEM97/σ2 receptor in breast cancer cell proliferation and responses to chemotherapy

Abstract

Abstract Introduction: Breast cancer is the most prevalent cancer for women both in the developed and the developing countries. In 2017, about 40,610 women are expected to die from breast cancer in the U.S. The sigma receptors (σRs) are transmembrane receptors with two subtypes, termed sigma-1 receptor and sigma-2 receptor. Sigma-2 receptor has been found overexpressed in numerous human cancer tissues, and compound targeting it are now in clinical trials for breast cancer diagnosis. But it's biological role in breast cancer is unknown because the encoded gene has not been clearly identified. Recently, it has been demonstrated that TMEM97, not progesterone Receptor Membrane Component 1 (PGRMC1), is a bona fide sigma-2 receptor. The identification of sigma-2 (σ2) receptor will make it possible to define its biological functions in breast cancer and develop modulator of σ2 receptor as potential cancer therapeutics. Methods: The expression of TMEM97/σ2 receptor in multiple cancer cells was evaluated by RT-qPCR. Regulation of P53 on TMEM97/σ2 receptor was determined by Western Blot after 48 hours Doxorubicin treatment of MCF7 cell and HCT116 wild type and P53-/- cells. PB28, an agonist of σ2 receptor and an antagonist of σ1 receptor, was used (0, 1μM, 10μM and 20μM for 4 days) to test its effects on MCF7 cell growth and colony formation. TMEM97/σ2 receptor was cloned and sequenced. We overexpressed TMEM97/σ2 receptor in MCF7 cells to characterize its role in cell proliferation, survival, and colony formation, with or without treatment of its agonist PB28. Results and conclusion: TMEM97/σ2 receptor is expressed in various cancer cell lines including lung, breast and prostate cancer, albeit at different levels. TMEM97 expression was reduced in MCF7 cells when p53 expression was stimulated by doxorubicin. PB28 reduced the number of viable cells and also reduced colony formation of MCF7 cells in a dose dependent manner. Meanwhile overexpression of TMEM97/σ2 receptor retarded cell growth in MCF7 cells and sensitized them to PB28 as evidenced by reduced IC50 when compared with control cells. The data suggest that TMEM97/σ2 receptor is expressed in breast cancer cells, with its expression suppressed by p53, and activation of this receptor led to reduced tumor cell proliferation. Citation Format: Yuanqin Zhang, Jiuhui Wang, Daotai Nie. Role of TMEM97/σ2 receptor in breast cancer cell proliferation and responses to chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2502.