Abstract P6-04-18: The regulatory role of activating transcription factor-2 (ATF2) in modulating tamoxifen resistance in estrogen-receptor positive breast cancer

摘要: Introduction: Activating transcription factor-2 (ATF2), a member of the ATF and CREB group bZIP factors regulates gene by forming homodimers or heterodimers with other AP-1 family members. We have previously shown that ATF2 is important for modulating effect tamoxifen, whereas Thr71-ATF2 phosphorylation predicts improved outcome ER-positive breast cancers receiving tamoxifen. In this study we further explore role in cancer endocrine therapy resistance. Methods: silencing: The MCF7, TamR, LCC2, LCC9 cell lines were maintained their appropriate growth media. Cells transfected using RNAiMAX (ThermoFisher Scientific) two different siRNAs Silencer® negative control. Gene expression was assessed quantitative real-time PCR (RT-qPCR) (TaqMan assays, ThermoFisher protein levels analysed western blotting. Cell growth, invasion, migration: Sulforhodamine B assay used determination following manufactures’ protocol. Soft-agar colony formation performed seeding incubating cells low-melting agarose plates. resulting colonies 5% MTT-stained counted Gel Count™ (Oxford Optronix). Invasion/migration transwell matrigel-coated (BD Biosciences) plates scratch wound healing assay. All assays triplicates three independent experiments. Microarray profiling: Human HT12_V4 microarray (Illumina) to identify genes differentially regulated ATF-2 silencing TamR compared MCF-7. Data analyses including log2 transformation quantile normalisation on R Bioconductor. Differentially-expressed selected FDR correction multiple testing p-value cut-off Results: significantly inhibited proliferation (p Conclusions: conclusion, first time, identified as novel factor can modulate resistance regulating ER activity. This data suggests may overcome highlights dual mediate sensitivity Citation Format: Athina Giannoudis, Mohammed I Malki, Hisham Mohammed, Bharath Rudraraju, Suraj Menon, Simak Ali, Jason S Carroll, Carlo Palmieri. regulatory activating (ATF2) tamoxifen estrogen-receptor positive [abstract]. In: Proceedings 2019 San Antonio Breast Cancer Symposium; Dec 10-14; Antonio, TX. Philadelphia (PA): AACR; Res 2020;80(4 Suppl):Abstract nr P6-04-18.