title: Prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system.
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.
authors: Department of Agronomy, Biometry Division, National Taiwan University, Taipei, Taiwan.
authors: Li-Yu D
authors: LY
authors: Liu
authors: Department of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan.
authors: Li-Yun
authors: LY
authors: Chang
authors: Department of Surgery, National Taiwan University, Taipei, Taiwan.
authors: Wen-Hung
authors: WH
authors: Kuo
authors: Department of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan.
authors: Hsiao-Lin
authors: HL
authors: Hwa
authors: Welgene Biotech. Co., Ltd., Taipei, Taiwan.
authors: Yi-Shing
authors: YS
authors: Lin
authors: Department of Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Meei-Huey
authors: MH
authors: Jeng
authors: Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA.
authors: Don A
authors: DA
authors: Roth
authors: Department of Surgery, National Taiwan University, Taipei, Taiwan. ; Cheng Ching General Hospital, Taichung, Taiwan.
authors: King-Jen
authors: KJ
authors: Chang
authors: Department of Obstetrics and Gynecology, National Taiwan University, Taipei, Taiwan. ; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan.
authors: Fon-Jou
authors: FJ
authors: Hsieh
keywords: STAT3 transcriptional regulatory network; TAM resistance; breast cancer; prognosis; tumorigenesis