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REVIEW: Estrogen Receptors, Antiestrogens, and Non-Small Cell Lung Cancer

T. A. Bogush1*, E. A. Dudko1, A. A. Beme1,2, E. A. Bogush1, A. I. Kim3, B. E. Polotsky1, S. A. Tjuljandin1, and M. I. Davydov1

1Blokhin Russian Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478 Moscow, Russia; fax: (495) 932-8568; E-mail: bogush@orc.ru

2Faculty of Fundamental Medicine, Lomonosov Moscow State University, 119192 Moscow, Russia

3Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

* To whom correspondence should be addressed.

Received June 20, 2010; Revision received July 12, 2010
This review considers data on expression of different types of estrogen receptors (ERα and ERβ) in in vitro cultured cells of non-small cell lung cancer and also in human and animal lung tumors. Estrogens are shown to play an important role in genesis and development of non-small cell lung cancer because the estrogen-stimulated cell proliferation as well as antiestrogen-caused inhibition of proliferation occurred only in the cells expressing different types of estrogen receptors. In general, the situation is similar to that observed in breast cancer, but in the cells of non-small cell lung cancer not ERα are expressed in more than half of cases but ERβ. Just estrogen receptors β play the crucial role in inducing cell proliferation in response to estrogens, and ERβ is a prognostic marker of a favorable course of non-small cell lung cancer. Data on the interactions between ER and EGFR signaling pathways, as well as on the additive antitumor effect of antiestrogens (tamoxifen and fulvestrant) combined with tyrosine kinase inhibitors (gefitinib, erlotinib, and vandetanib) are considered. The review also includes data on the influence of estrogens on genesis and development of lung cancer in humans and animals and the frequency of ERα and ERβ expression in non-small cell lung cancer in tissues from patients of the two sexes. Problems of quantitative determination of α and β estrogen receptors in the tumor cells are also discussed.
KEY WORDS: estrogen receptors, non-small cell lung cancer, antiestrogens

DOI: 10.1134/S0006297910120011