biostudies-literatureUnknown9(30)Kimura MWe previously reported the establishment of several types of long-term estrogen-depleted-resistant (EDR) cell lines from MCF-7 breast cancer cells. Type 1 EDR cells exhibited the best-studied mechanism of aromatase inhibitor (AI) resistance, in which estrogen receptor (ER) expression remained positive and PI3K signaling was upregulated. Type 2 EDR cells showed reduced ER activity and upregulated JNK-related signaling. The mTOR inhibitor everolimus reduced growth in cells similar to Type 1 EDR cells. The present study generated everolimus-resistant (EvR) cells from Types 1 and 2 EDR cells following long-term exposure to everolimus <i>in vitro</i>. These EvR cells modeled resistance to AI and everolimus combination therapies following first-line AI treatment failure. In Type 1 EvR cells, eveOncotarget21468-21477https://www.ebi.ac.uk/biostudies/studies/S-EPMC5940386biostudies-literatureAcquired resistance to everolimus in aromatase inhibitor-resistant breast cancer.PMC5940386Niwa TKaneko YHayashi SIEndo INarui KYamaguchi YKimura MHanamura TTsuboi KfalseAcquired resistance to everolimus in aromatase inhibitor-resistant breast cancer.We previously reported the establishment of several types of long-term estrogen-depleted-resistant (EDR) cell lines from MCF-7 breast cancer cells. Type 1 EDR cells exhibited the best-studied mechanism of aromatase inhibitor (AI) resistance, in which estrogen receptor (ER) expression remained positive and PI3K signaling was upregulated. Type 2 EDR cells showed reduced ER activity and upregulated JNK-related signaling. The mTOR inhibitor everolimus reduced growth in cells similar to Type 1 EDR cells. The present study generated everolimus-resistant (EvR) cells from Types 1 and 2 EDR cells following long-term exposure to everolimus <i>in vitro</i>. These EvR cells modeled resistance to AI and everolimus combination therapies following first-line AI treatment failure. In Type 1 EvR cells, eve2018-01-01T00:00:00Z2018 Apr2025-04-05T10:57:21.697Z2019-03-26T23:37:40ZS-EPMC59403862976555310.18632/oncotarget.25133