Prominent oncogenic roles of EVI1 in breast carcinoma

Hui Wang, Thorsten Schaefer, Martina Konantz, Martin Braun, Zsuzsanna Varga, Anna M. Paczulla, Selina Reich, Francis Jacob, Sven Perner, Holger Moch, Tanja N. Fehm, Lothar Kanz, Klaus Schulze-Osthoff, Claudia Lengerke*

*Corresponding author for this work
21 Citations (Scopus)


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.

Original languageEnglish
JournalCancer Research
Issue number8
Pages (from-to)2148-2160
Number of pages13
Publication statusPublished - 15.04.2017


Dive into the research topics of 'Prominent oncogenic roles of EVI1 in breast carcinoma'. Together they form a unique fingerprint.

Cite this