biostudies-literatureUnknown8(1)Ventura-Bixenshpaner HAcquired resistance to the estrogen receptor (ER) antagonist tamoxifen, is a major obstacle in treatment of breast cancer. Changes in Zn²⁺ accumulation and distribution are associated with tamoxifen-resistance and breast cancer progression. The Zn²⁺-sensing G-protein coupled receptor, ZnR/GPR39, triggers signaling leading to cell growth, but a role for this receptor in breast cancer in unknown. Using fluorescence imaging, we found Zn²⁺-dependent Ca²⁺ release, mediated by ZnR/GPR39 activity, in TAMR tamoxifen-resistant cells derived from MCF-7 cells, but not in ER-expressing MCF-7 or T47D cells. Furthermore, ZnR/GPR39 signaling was monitored in ER negative BT20, MDA-MB-453 and JIMT-1 cells. Expression of ZnR/GPR39 was increased in grade 3 human brScientific reports8119https://www.ebi.ac.uk/biostudies/studies/S-EPMC5970167biostudies-literatureEnhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth.PMC5970167Sekler IElkabets MAsraf HTaylor KMVentura-Bixenshpaner HChakraborty MHershfinkel MfalseEnhanced ZnR/GPR39 Activity in Breast Cancer, an Alternative Trigger of Signaling Leading to Cell Growth.Acquired resistance to the estrogen receptor (ER) antagonist tamoxifen, is a major obstacle in treatment of breast cancer. Changes in Zn²⁺ accumulation and distribution are associated with tamoxifen-resistance and breast cancer progression. The Zn²⁺-sensing G-protein coupled receptor, ZnR/GPR39, triggers signaling leading to cell growth, but a role for this receptor in breast cancer in unknown. Using fluorescence imaging, we found Zn²⁺-dependent Ca²⁺ release, mediated by ZnR/GPR39 activity, in TAMR tamoxifen-resistant cells derived from MCF-7 cells, but not in ER-expressing MCF-7 or T47D cells. Furthermore, ZnR/GPR39 signaling was monitored in ER negative BT20, MDA-MB-453 and JIMT-1 cells. Expression of ZnR/GPR39 was increased in grade 3 human br2018-01-01T00:00:00Z2018 May2026-07-15T17:02:13.812Z2019-03-26T23:39:30ZS-EPMC59701672980234810.1038/s41598-018-26459-5