PUBLICATION
Prominent Oncogenic Roles of EVI1 in Breast Carcinoma
- Authors
- Wang, H., Schaefer, T., Konantz, M., Braun, M., Varga, Z., Paczulla, A.M., Reich, S., Jacob, F., Perner, S., Moch, H., Fehm, T.N., Kanz, L., Schulze-Osthoff, K., Lengerke, C.
- ID
- ZDB-PUB-170512-11
- Date
- 2017
- Source
- Cancer research 77: 2148-2160 (Journal)
- Registered Authors
- Konantz, Martina, Lengerke, Claudia, Wang, Hui
- Keywords
- none
- MeSH Terms
-
- Animals
- Apoptosis/genetics
- Breast Neoplasms/genetics*
- Breast Neoplasms/metabolism
- Breast Neoplasms/pathology
- Cell Line, Tumor
- Cell Proliferation/genetics
- DNA-Binding Proteins/biosynthesis
- DNA-Binding Proteins/genetics*
- Female
- Gene Knockdown Techniques
- Heterografts
- Humans
- Immunohistochemistry
- Mice, Inbred NOD
- Mice, SCID
- Proto-Oncogenes/genetics*
- Receptor, ErbB-2/metabolism
- Receptors, Estrogen/metabolism
- Transcription Factors/biosynthesis
- Transcription Factors/genetics*
- Triple Negative Breast Neoplasms/genetics
- Triple Negative Breast Neoplasms/metabolism
- Zebrafish
- PubMed
- 28209621 Full text @ Cancer Res.
Citation
Wang, H., Schaefer, T., Konantz, M., Braun, M., Varga, Z., Paczulla, A.M., Reich, S., Jacob, F., Perner, S., Moch, H., Fehm, T.N., Kanz, L., Schulze-Osthoff, K., Lengerke, C. (2017) Prominent Oncogenic Roles of EVI1 in Breast Carcinoma. Cancer research. 77:2148-2160.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping