Vol 9: Increased STAT1 Signaling in Endocrine-Resistant Breast Cancer.Report as inadecuate

 Vol 9: Increased STAT1 Signaling in Endocrine-Resistant Breast Cancer.

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This article is from PLoS ONE, volume 9.AbstractProteomic profiling of the estrogen-tamoxifen-sensitive MCF-7 cell line and its partially sensitive MCF-7-LCC1 and fully resistant MCF-7-LCC9 variants was performed to identify modifiers of endocrine sensitivity in breast cancer. Analysis of the expression of 120 paired phosphorylated and non-phosphorylated epitopes in key oncogenic and tumor suppressor pathways revealed that STAT1 and several phosphorylated epitopes phospho-STAT1Tyr701 and phospho-STAT3Ser727 were differentially expressed between endocrine resistant and parental controls, confirmed by qRT-PCR and western blotting. The STAT1 inhibitor EGCG was a more effective inhibitor of the endocrine resistant MCF-7-LCC1 and MCF-7-LCC9 lines than parental MCF-7 cells, while STAT3 inhibitors Stattic and WP1066 were equally effective in endocrine-resistant and parental lines. The effects of the STAT inhibitors were additive, rather than synergistic, when tested in combination with tamoxifen in vitro. Expression of STAT1 and STAT3 were measured by quantitative immunofluorescence in invasive breast cancers and matched lymph nodes. When lymph node expression was compared to its paired primary breast cancer expression, there was greater expression of cytoplasmic STAT1 ∼3.1 fold, phospho-STAT3Ser727 ∼1.8 fold, and STAT5 ∼1.5 fold and nuclear phospho-STAT3Ser727 ∼1.5 fold in the nodes. Expression levels of STAT1 and STAT3 transcript were analysed in 550 breast cancers from publicly available gene expression datasets GSE2990, GSE12093, GSE6532. When treatment with tamoxifen was considered, STAT1 gene expression was nearly predictive of distant metastasis-free survival DMFS, log-rank p = 0.067, while STAT3 gene expression was predictive of DMFS log-rank p

Author: Huang, Rui; Faratian, Dana; Sims, Andrew H.; Wilson, Danielle; Thomas, Jeremy S.; Harrison, David J.; Langdon, Simon P.

Source: https://archive.org/

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