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Prominent Oncogenic Roles of EVI1 in Breast Carcinoma.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2017
Author Wang Hui, Schaefer Thorsten, Konantz Martina, Braun Martin, Varga Zsuzsanna, Paczulla Anna M, Reich Selina, Jacob Francis, Perner Sven, Moch Holger, Fehm Tanja N, Kanz Lothar, Schulze-Osthoff Klaus, Lengerke Claudia,
Project Role and molecular targets of the transcription factor EVI1 in lymphoblastic leukemia and blood stem cell development
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Original article (peer-reviewed)

Journal Cancer research
Volume (Issue) 77(8)
Page(s) 2148 - 2160
Title of proceedings Cancer research
DOI 10.1158/0008-5472.CAN-16-0593


Overexpression of the EVI1 oncogene is associated typically with aggressive myeloid leukemia, but is also detectable in breast carcinoma where its contributions are unexplored. Analyzing a tissue microarray of 608 breast carcinoma patient specimens, we documented EVI1 overexpression in both estrogen receptor-positive (ER(+)) and estrogen receptor-negative (ER(-)) breast carcinomas. Here, we report prognostic relevance of EVI1 overexpression in triple-negative breast carcinoma but not in the HER2-positive breast carcinoma subset. In human breast cancer cells, EVI1 silencing reduced proliferation, apoptosis resistance, and tumorigenicity, effects rescued by estrogen supplementation in ER(+) breast carcinoma cells. Estrogen addition restored ERK phosphorylation in EVI1-silenced cells, suggesting that EVI1 and estradiol signaling merge in MAPK activation. Conversely, EVI1 silencing had no effect on constitutive ERK activity in HER2(+) breast carcinoma cells. Microarray analyses revealed G-protein-coupled receptor (GPR) signaling as a prominent EVI1 effector mechanism in breast carcinoma. Among others, the GPR54-ligand KISS1 was identified as a direct transcriptional target of EVI1, which together with other EVI1-dependent cell motility factors such as RHOJ regulated breast carcinoma cell migration. Overall, our results establish the oncogenic contributions of EVI1 in ER- and HER2-negative subsets of breast cancer. Cancer Res; 77(8); 2148-60. ©2017 AACR.