Cytoplasmic estrogen receptor β as a potential marker in human non-small cell lung carcinoma

Mohit Kumar Verma, Yasuhiro Miki, Keiko Abe, Hiromichi Niikawa, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)S91-S102
JournalExpert Opinion on Therapeutic Targets
Issue numberSUPPL. 1
Publication statusPublished - 2012 Mar


  • Aromatase
  • Estrogen receptor
  • Lung carcinoma
  • MAPK inhibitor
  • Non-genomic

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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