Estrogen adversely affects the prognosis of patients with lung adenocarcinoma

Li Han Hsu, Ko Jiunn Liu, Ming Fang Tsai, Chang Ru Wu, An Chen Feng, Nei Min Chu, Shu Huei Kao

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Estrogen has been postulated to contribute to the development and progression of lung cancer. We examined the epidemiologic evidence, explored the characteristics of estrogen receptors (ER) in lung adenocarcinoma, and investigated the effect of estrogen on lung cancer cell migration, including the signaling pathway involved. For epidemiologic evidence, a total of 1434 consecutive non-small cell lung cancer patients who underwent standardized staging and homogenous treatment were prospectively enrolled from January 2002 to December 2008, and followed until December 2012. The possible prognostic factors to be analyzed included stage, age, gender, menopausal status, smoking history and histology. For laboratory study, lung cancer cell lines A549 and PE089 and malignant pleural effusions from the patients with lung adenocarcinoma were used. We found that the premenopausal patients had more advanced disease and a shorter survival among the never-smoking female patients with lung adenocarcinoma. ERβ was the predominant ER in the lung cancer cell lines. We proposed a different pathway that estrogen upregulated the expression of osteopontin and then promoted cell migration through αvβ3 integrin binding and activated MEK-ERK signaling pathway, which is a common downstream pathway with epidermal growth factor receptor (EGFR) activation. An additive effect of ER antagonists and EGFR antagonists on the inhibition of cell migration was also noted. Our results suggest that estrogen adversely affects the prognosis of patients with lung adenocarcinoma. Osteopontin contributed to the cross-talk between ER and EGFR signaling pathways. Estrogen, with its receptor, has the potential to be a prognosticator and a therapeutic target in lung cancer. Estrogen up-regulates osteopontin expression and promotes lung cancer cell migration via the MEK/ERK signaling pathway. Osteopontin contributes to the cross-talk between estrogen receptor and epidermal growth factor receptor signaling pathways.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalCancer Science
Volume106
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Lung Neoplasms
Estrogens
Osteopontin
Estrogen Receptors
Epidermal Growth Factor Receptor
Cell Movement
MAP Kinase Signaling System
Smoking
Cell Migration Inhibition
Malignant Pleural Effusion
Integrins
Non-Small Cell Lung Carcinoma
Adenocarcinoma of lung
Histology
Up-Regulation
History
Cell Line
Survival
Therapeutics

Keywords

  • Epidermal growth factor receptor
  • Estrogen
  • Estrogen receptor
  • Lung cancer
  • Osteopontin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Hsu, L. H., Liu, K. J., Tsai, M. F., Wu, C. R., Feng, A. C., Chu, N. M., & Kao, S. H. (2015). Estrogen adversely affects the prognosis of patients with lung adenocarcinoma. Cancer Science, 106(1), 51-59. https://doi.org/10.1111/cas.12558

Estrogen adversely affects the prognosis of patients with lung adenocarcinoma. / Hsu, Li Han; Liu, Ko Jiunn; Tsai, Ming Fang; Wu, Chang Ru; Feng, An Chen; Chu, Nei Min; Kao, Shu Huei.

In: Cancer Science, Vol. 106, No. 1, 01.01.2015, p. 51-59.

Research output: Contribution to journalArticle

Hsu, LH, Liu, KJ, Tsai, MF, Wu, CR, Feng, AC, Chu, NM & Kao, SH 2015, 'Estrogen adversely affects the prognosis of patients with lung adenocarcinoma', Cancer Science, vol. 106, no. 1, pp. 51-59. https://doi.org/10.1111/cas.12558
Hsu LH, Liu KJ, Tsai MF, Wu CR, Feng AC, Chu NM et al. Estrogen adversely affects the prognosis of patients with lung adenocarcinoma. Cancer Science. 2015 Jan 1;106(1):51-59. https://doi.org/10.1111/cas.12558
Hsu, Li Han ; Liu, Ko Jiunn ; Tsai, Ming Fang ; Wu, Chang Ru ; Feng, An Chen ; Chu, Nei Min ; Kao, Shu Huei. / Estrogen adversely affects the prognosis of patients with lung adenocarcinoma. In: Cancer Science. 2015 ; Vol. 106, No. 1. pp. 51-59.
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