Abstract P6-07-10: The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling

Triple negative breast cancer (TNBC) still remains a challenge to treat in the clinic due to a lack of good targets for treatment. Although TNBC lacks expression of ERα, the expression of ERβ and its variants are detected quite frequently in this cancer type and can represent an avenue for treatment. We show that the variants of ERβ, namely ERβ1, ERβ2, ERβ4, and ERβ5, regulate aggressiveness of TNBC by regulating hypoxic signaling. RNA-seq of patient derived xenografts (PDX) from TNBC show expression of ERβ4 and ERβ5 variants in more than half of the samples. Furthermore, expression of ERβ4 in the immortalized, normal mammary epithelial cell line MCF-10A that is resistant to mammosphere formation caused transformation and development of mammospheres. By contrast, ERβ1, ERβ2 or ERβ5 were unable to support mammosphere formation. We have previously shown that all variants except ERβ1 stabilizes HIF-1α but only ERβ4 appear to have the ability to transform normal mammary epithelial cells, pointing towards a unique property of ERβ4. We propose that ERβ variants may be good diagnostic tools and also serve as novel targets for treatment of breast cancer. Citation Format: Faria M, Karami S, Granados-Principal S, Dey P, Verma A, Choi DS, Elemento O, Bawa-Khalfe1 T, Chang JC, Gustafsson J-A, Strom AM. The ERβ4 variant induce transformation of the normal breast mammary epithelial cell line MCF-10A; the ERβ variants ERβ2, ERβ4 and ERβ5 increase aggressiveness of TNBC by regulation of hypoxic signaling [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-07-10.