Tamoxifen, an antagonist of the estrogen receptor (ER), is a therapeutic agent currently used for the breast cancer patients with ER-positive tumors 1,2. The use of this endocrine therapeutic drug has significantly improved disease free survival and overall survival of the patients 1,3. But acquired tamoxifen resistance is still the main reason for endocrine therapy failure and subsequent cancer recurrence and cancer-related death 1,4. Actually , the mechanism of tamoxifen resistance is quite

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... mplex and is far from been fully understood. Extracellular vesicles, such as exosomes and microvesicles can transport coding and non-coding RNAs, proteins and lipids, thereby acting a potential mode of intercellular communication 5. Some recent papers reported that exosomes are involved in the regulation of chemosensitivity of the recipient cells. In human hepatocellular cancer , exosomes mediated transfer of long non-coding RNA (lncRNA) ROR can increase chemore-sistance 6,7. In breast cancer, exosomal transfer of miR-221/222 can enhance tamoxifen resistance in recipient ER-positive breast cancer cells 8. LncRNAs are evolutionarily conserved non-protein coding RNAs greater than 200 nucleotides 9. Dysregulated lncRNAs RNAs is also a mechanism of tamoxifen resistance development in breast cancer. One recent study found HOTAIR overexpression can activate the ER transcriptional program even under hormone-deprived conditions and promote Abstract.-OBJECTIVE: In this study, we firstly compared the loading of urothelial carcino-ma-associated 1 (UCA1) in exosomes between tamoxifen sensitive and tamoxifen resistant breast cancer cells and further investigated the role of exosomal transfer of UCA1 in the development of tamoxifen resistance in estrogen receptor (ER) positive breast cancer cells. MATERIALS AND METHODS: Exosomes were isolated from the culture medium of tamoxifen sensitive MCF-7 cells and tamoxifen resistant LCC2 cells. QRT-PCR was performed to analyze UCA1 expression in cells and exosomes. CCK-8 assay, immunofluorescence staining of cleaved caspase-3 and flow cytometric analysis of an-nexin V/PI staining were used to assess tamoxi-fen sensitivity. RESULTS: UCA1 is significantly increased not only in LCC2 cells, but also in exosomes released from LCC2 cells. The increase in exo-somes is more evident than in cells. MCF-7 cells pretreated with exos/LCC2 had a significantly increased cell viability, a decreased expression of cleaved caspase-3 and a lower ratio of apoptosis after tamoxifen treatment. The exos/LCC2 with impaired UCA1 loading had significantly suppressed capability to promote tamoxifen resistance in MCF-7 cells. CONCLUSIONS: UCA1 is significantly loaded in exosomes from tamoxifen resistant LCC2 cells. Exosomes mediated transfer of UCA1 can significantly increase tamoxifen resistance in ER-positive MCF-7 cells.