| Autor: |
Semina SE; N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia. s.e.semina@gmail.com., Scherbakov AM; N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia. alex.scherbakov@gmail.com., Vnukova AA; Faculty of Preventive Medicine, I.M. Sechenov First Moscow State Medical University, Trubetskaya Street 8-2, Moscow 119991, Russia. biochem.fan@ya.ru., Bagrov DV; Faculty of Biology, Lomonosov Moscow State University, 1/12, Leninskie gory, Moscow 119234, Russia. dbagrov@gmail.com., Evtushenko EG; Faculty of Chemistry, Lomonosov Moscow State University, 1/3, Leninskie gory, Moscow 119234, Russia. evtushenko@enzyme.chem.msu.ru., Safronova VM; N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia. vera.svm@gmail.com., Golovina DA; N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia. dar.golovina@gmail.com., Lyubchenko LN; N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia. clingen@mail.ru., Gudkova MV; N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia. gudkova@ronc.ru., Krasil'nikov MA; N.N. Blokhin National Medical Research Center of Oncology, Kashirskoye shosse 24, Moscow 115478, Russia. krasilnikovm1@ya.ru. |
| Abstrakt: |
Exosomes are small vesicles which are produced by the cells and released into the surrounding space. They can transfer biomolecules into recipient cells. The main goal of the work was to study the exosome involvement in the cell transfer of hormonal resistance. The experiments were performed on in vitro cultured estrogen-dependent MCF-7 breast cancer cells and MCF-7 sublines resistant to SERM tamoxifen and/or biguanide metformin, which exerts its anti-proliferative effect, at least in a part, via the suppression of estrogen machinery. The exosomes were purified by differential ultracentrifugation, cell response to tamoxifen was determined by MTT test, and the level and activity of signaling proteins were determined by Western blot and reporter analysis. We found that the treatment of the parent MCF-7 cells with exosomes from the resistant cells within 14 days lead to the partial resistance of the MCF-7 cells to antiestrogen drugs. The primary resistant cells and the cells with the exosome-induced resistance were characterized with these common features: decrease in ERα activity and parallel activation of Akt and AP-1, NF-κB, and SNAIL1 transcriptional factors. In general, we evaluate the established results as the evidence of the possible exosome involvement in the transferring of the hormone/metformin resistance in breast cancer cells. |
