Genomics

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The inferred mechanisms for prognostic features of signal transducer and activator of transcription 3 in an ER(+) breast cancer model system


ABSTRACT: Abstract Aberrantly expressed signal transducer and activator of transcription 3 (STAT3) predicts poor prognosis primarily in estrogen receptor positive (ER(+)) breast cancers and 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-ER , STAT3-MYC-ER interactions and the direct action of activated STAT3. These results predict malignant events, treatment responses and a novel enhancer of tamoxifen resistance. The inferred crosstalk between ER 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, prognosis, tamoxifen resistance, tumorigenesis, breast cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24124 | GEO | 2010/11/04

SECONDARY ACCESSION(S): PRJNA130065

REPOSITORIES: GEO

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