RT Journal Article SR Electronic T1 Estrogen Receptor β Is Involved in Acquired Resistance to EGFR-tyrosine Kinase Inhibitors in Lung Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2371 OP 2381 DO 10.21873/anticanres.15012 VO 41 IS 5 A1 HIROKI SUGIURA A1 YASUHIRO MIKI A1 ERINA IWABUCHI A1 RYOKO SAITO A1 KATSUHIKO ONO A1 IKURO SATO A1 YOSHINORI OKADA A1 HIRONOBU SASANO YR 2021 UL http://ar.iiarjournals.org/content/41/5/2371.abstract AB Background/Aim: Acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has posed serious clinical problems in the treatment of lung adenocarcinoma (LADC) patients harboring relevant EGFR mutations. In this study, we explored the role of estrogen receptor β (ERβ) in the development of acquired resistance to EGFR-TKIs in human LADC. Materials and Methods: First, the role of ERβ in erlotinib resistance of LADC cell lines (PC9/ER) was examined. Then, the immunolocalization of ERβ in 28 LADC patient samples treated with EGFR-TKIs was investigated. Results: Cytoplasmic ERβ was upregulated in erlotinib resistant cell lines. EGFR-TKIs sensitivity increased with ERβ inhibition in PC9/ER cells. ERK1/2 and AKT activities were both markedly increased by specific ERβ agonists even under erlotinib treatment of PC9/ER cells. Cytoplasmic ERβ immunoreactivity was significantly associated with clinical response to EGFR-TKIs. Conclusion: Cytoplasmic ERβ in LADC cells was involved in the development of resistance to EGFR-TKIs.