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Updated: May 25, 2026
Screening for Phytoestrogens using a Cell-based Estrogen Receptor β Reporter Assay
Published on: June 7, 2020
Cytoplasmic estrogen receptor β as a potential marker in human non-small cell lung carcinoma
Mohit Kumar Verma1, Yasuhiro Miki, Keiko Abe
1Tohoku University Graduate School of Medicine, Department of Pathology, 2-1 Seriyo-machi, Aoba-ku, Sendai, Miyagi-ken 980 8575, Japan.
Objectives:
Estrogen has been reported to promote an increased susceptibility to lung cancer development. This study focusses on the role of cytoplasmic estrogen receptor β (c-ERβ) in NSCLC.
Methods:
NSCLC (n = 162) cases were analyzed using immunohistochemistry (IHC) for c-ERβ expression and its association with clinicopathological variables. Significance of c-ERβ expression was further examined using in vitro studies in NSCLC cell lines.
Results:
Among ERβ and aromatase positive NSCLC females, c-ERβ was significantly associated with greater tumor diameter and tended to be associated with worse overall survival. A549 and LCAM1 cells expressed aromatase, as well as c-ERβ and nuclear ERβ (n-ERβ). U0126 (MAPK/extracellular-signal-regulated kinase (ERK) inhibitor) abrogated MAPK phosphorylation, caused by estradiol via c-ERβ, more effectively than ICI 182780 (ER blocker) in either cell line. However, ICI 182780 completely abrogated the estrogen responsive elements (ERE)-luciferase activity caused by estradiol. Combination therapy with ICI 182780 and U0126 turned out to be far more effective than either treatment alone in either A549 or LCAM1 cells.
Conclusion:
The results indicated that ERβ may contribute to NSCLC via non-genomic action of estrogen through its cytoplasmic form, in addition to the genomic actions via n-ERβ. These actions of estrogen in NSCLCs may be abrogated by combination therapy with ICI 182780 and U0126.
