Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system
Journal
Cancer Informatics
Journal Volume
13
Pages
21-45
Date Issued
2014
Author(s)
Chang, L.-Y.
Lin, Y.-S.
Jeng, M.-H.
Roth, D.A.
Abstract
The aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis, primarily in estrogen receptor positive (ER(+)) breast cancers. Activated STAT3 is overexpressed in luminal A subtype cells. The mechanisms contributing to the prognosis and/or subtype relevant features of STAT3 in ER(+) breast cancers are through multiple interacting regulatory pathways, including STAT3-MYC, STAT3-ERα, and STAT3-MYC-ERα interactions, as well as the direct action of activated STAT3. These data predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ERα and STAT3 in regulating their shared target gene-METAP2 is partially validated in the luminal B breast cancer cell line-MCF7. Taken together, we identify a poor prognosis relevant gene set within the STAT3 network and a robust one in a subset of patients. VEGFA, ABL1, LYN, IGF2R and STAT3 are suggested therapeutic targets for further study based upon the degree of differential expression in our model. © the author(s), publisher and licensee Libertas Academica Ltd.
SDGs
Publisher
Libertas Academica Ltd.
Type
journal article