Fulvestrant-mediated inhibition of estrogen receptor signaling slows lung cancer progression.

Abstract

Estrogens are key signaling molecules that regulate various physiological processes such as cell growth, development, and differentiation. They also play a major role in many pathological conditions, such as hormone-dependent cancer. The importance of inhibiting estrogen receptor signaling in diseases of estrogen target tissues, such as breast cancer, is well documented. However, the role of estrogen signaling in diseases of nontarget tissues, such as lung cancer, is not well characterized. The aim of the current study is to examine the expression of estrogen receptor β (ERβ) and the roles of estradiol (E2) and fulvestrant on the progression of lung cancer. Tissue microarray (TMA) and immunohistochemistry (IHC) analyses were used to detect the expression of aromatase, ERα, and ERβ in 198 patients. We performed analyses to determine if there was any correlation among these three proteins. A mouse model of urethane-induced lung adenocarcinoma was used in the study. Mice were divided into three treatment groups: blank control, E2 alone, and E2 + fulvestrant (ERβ antagonist). Western blot analysis and fluorescence quantitative PCR (FQ-PCR) were used to measure expression of ERβ protein and mRNA levels, respectively. ERβ, but not ERα, was overexpressed in NSCLC samples. Lung cancer progression in mice treated with E2 was significantly increased compared to either the control group or the E2 + fulvestrant group. Mice in the E2 treatment group had significantly increased expression of ERβ at both the mRNA and protein levels compared to mice treated with E2 + fulvestrant or control. Our data suggest that ERβ promotes lung cancer progression in mice and that this progression can be inhibited with fulvestrant. These findings may help elucidate the role of ERβ in lung cancer and suggest that estrogen receptor antagonists, such as fulvestrant, may be therapeutically beneficial for the treatment of the disease.

• Authors: Hexiao Tang, Yongde Liao, Chao Zhang, Guang Chen, Liqiang Xu, Zhaoguo Liu, Shengling Fu, Li Yu, Sheng Zhou
• Journal: Oncology research (Oncol Res) Vol. 22 Issue 1 Pg. 13-20 ( 2014) ISSN: 1555-3906 [Electronic] United States
• PMID: 25700354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Hormonal
• Estrogen Receptor alpha
• Estrogen Receptor beta
• Fulvestrant
• Urethane
• Estradiol

Topics

• Adenocarcinoma (chemically induced, drug therapy)
• Adult
• Aged
• Animals
• Antineoplastic Agents, Hormonal (administration & dosage, adverse effects)
• Carcinogenesis (drug effects)
• Disease Models, Animal
• Estradiol (administration & dosage, adverse effects, analogs & derivatives, metabolism)
• Estrogen Receptor alpha (metabolism)
• Estrogen Receptor beta (antagonists & inhibitors, metabolism)
• Female
• Fulvestrant
• Humans
• Immunohistochemistry
• Lung Neoplasms (chemically induced, drug therapy)
• Male
• Mice
• Mice, Inbred Strains
• Middle Aged
• Signal Transduction (drug effects)
• Tissue Array Analysis
• Urethane (administration & dosage)