Estrogen receptor β is involved in acquired resistance to egfr-Tyrosine kinase inhibitors in lung cancer

Hiroki Sugiura, Yasuhiro Miki, Erina Iwabuchi, Ryoko Saito, Katsuhiko Ono, Ikuro Sato, Yoshinori Okada, Hironobu Sasano

研究成果: Article査読

1 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2371-2381
ページ数11
ジャーナルAnticancer research
41
5
DOI
出版ステータスPublished - 2021 5

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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