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Cancer Inform. 2014 Jan 21;13:21-45. doi: 10.4137/CIN.S12493. eCollection 2014.

Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system.

Author information

1
Department of Agronomy, Biometry Division, National Taiwan University, Taipei, Taiwan.
2
Department of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan.
3
Department of Surgery, National Taiwan University, Taipei, Taiwan.
4
Welgene Biotech. Co., Ltd., Taipei, Taiwan.
5
Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
6
Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
7
Department of Surgery, National Taiwan University, Taipei, Taiwan. ; Cheng Ching General Hospital, Taichung, Taiwan.
8
Department of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan. ; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.

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.

KEYWORDS:

STAT3 transcriptional regulatory network; TAM resistance; breast cancer; prognosis; tumorigenesis

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