Estrogen Receptor β Is Involved in Acquired Resistance to EGFR-tyrosine Kinase Inhibitors in Lung Cancer.

Abstract

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.

• Authors: Hiroki Sugiura, Yasuhiro Miki, Erina Iwabuchi, Ryoko Saito, Katsuhiko Ono, Ikuro Sato, Yoshinori Okada, Hironobu Sasano
• Journal: Anticancer research (Anticancer Res) Vol. 41 Issue 5 Pg. 2371-2381 (May 2021) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33952462 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Estrogen Receptor beta
• Estrogens
• Protein Kinase Inhibitors
• Estradiol
• Erlotinib Hydrochloride
• ErbB Receptors

Topics

• A549 Cells
• Adenocarcinoma (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Survival (drug effects, genetics)
• Drug Resistance, Neoplasm (genetics)
• ErbB Receptors (antagonists & inhibitors, genetics, metabolism)
• Erlotinib Hydrochloride (pharmacology)
• Estradiol (pharmacology)
• Estrogen Receptor beta (genetics, metabolism)
• Estrogens (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lung Neoplasms (genetics, metabolism, pathology)
• Protein Kinase Inhibitors (pharmacology)
• RNA Interference