Estrogen Receptors Β — New Target in Cellular Lung Cancer Treatment

Давыдов, М. И.; Богуш, Т. А.; Полоцкий, Б. Е.; Tyulyandin, S. A.

doi:10.15690/vramn.v67i2.118

Cited by 8 publications

(3 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results are consistent with the in vitro findings that estrogen potentiates the proliferation of lung cancer cells . Although discovered in the mid‐1990s, the molecular mechanisms of ERβ in lung cancer are poorly understood, and the effect of estrogen signaling on the progression of lung cancer may be associated with other signaling pathways . For example, Majidi et al .…”

Section: Discussionsupporting

confidence: 87%

“…Many studies have reported that IGF‐1R inhibitors may have an inhibitory effect on lung cancer, although several clinical trials of IGF‐1R inhibitors in unselected patients have been discontinued because of high toxicities or an unlikelihood of meeting the primary endpoint . This negative effect may be associated with the multisignaling pathways involved in lung cancer . Based on the finding that estrogen upregulates the IGF‐1 signaling pathway in lung cancer, it remains unclear whether an interaction between ERβ and IGF‐1R is involved in the malignant development of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Estrogen and insulin‐like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice

Tang

Liao

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

Estrogen receptor (ER) and insulin‐like growth factor‐1 receptor (IGF‐1R) signaling are implicated in lung cancer progression. Based on their previous findings, the authors sought to investigate whether estrogen and IGF‐1 act synergistically to promote lung adenocarcinoma (LADE) development in mice. LADE was induced with urethane in ovariectomized Kunming mice. Tumor‐bearing mice were divided into seven groups: 17β‐estradiol (E2), E2+fulvestrant (Ful; estrogen inhibitor), IGF‐1, IGF‐1+AG1024 (IGF‐1 inhibitor), E2+IGF‐1, E2+IGF‐1+Ful+AG1024 and control groups. After 14 weeks, the mice were sacrificed, and then the tumor growth was determined. The expression of ERα/ERβ, IGF‐1, IGF‐1R and Ki67 was examined using tissue‐microarray‐immunohistochemistry, and IGF‐1, p‐ERβ, p‐IGF‐1R, p‐MAPK and p‐AKT levels were determined based on Western blot analysis. Fluorescence‐quantitative polymerase chain reaction was used to detect the mRNA expression of ERβ, ERβ2 and IGF‐1R. Tumors were found in 93.88% (46/49) of urethane‐treated mice, and pathologically proven LADE was noted in 75.51% (37/49). In the E2+IGF‐1 group, tumor growth was significantly higher than in the E2 group (p < 0.05), the IGF‐1 group (p < 0.05) and control group (p < 0.05). Similarly, the expression of ERβ, p‐ERβ, ERβ2, IGF‐1, IGF‐1R, p‐IGF‐1R, p‐MAPK, p‐AKT and Ki67 at the protein and/or mRNA levels was markedly higher in the ligand group than in the ligand + inhibitor groups (all p < 0.05). This study demonstrated for the first time that estrogen and IGF‐1 act to synergistically promote the development of LADE in mice, and this may be related to the activation of the MAPK and AKT signaling pathways in which ERβ1, ERβ2 and IGF‐1R play important roles.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Estrogen and insulin‐like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice

Tang

Liao

et al. 2013

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…Since many of the genes that ER regulates promote cellular proliferation, ERβ may be a useful therapeutic target in certain cancers. Although discovered in the mid-1990s, the molecular mechanisms of ERβ action in lung cancer are poorly understood, and effect of antiestrogen therapy for the treatment of lung cancer is of great interest ( 9,10 ).…”

Section: Introductionmentioning

confidence: 99%

Fulvestrant-Mediated Inhibition of Estrogen Receptor Signaling Slows Lung Cancer Progression

Tang¹,

Liao²,

Zhang³

et al. 2014

oncol res

View full text Add to dashboard Cite

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.

show abstract

The co-expression of ERβ2 and IL-12Rβ2 is better prognostic factor in non-small-cell lung cancer progression

Liu¹,

Lei²,

Li³

et al. 2013

Med Oncol

View full text Add to dashboard Cite

Estrogens and IL-12 play a pivotal role in the development and progression of non-small-cell lung cancer (NSCLC); at the same time, estrogen receptor β2 and (interleukin-12 receptor β2)IL-12Rβ2 are their important receptors, respectively. With the functions of ERβ2 and IL-12Rβ2 explored further in NSCLC, some questions on the relation between ERβ2 and IL-12Rβ2 expression need to be solved. In this study, our aim is to elucidate relationship and roles of ERβ2 and IL-12Rβ2 in NSCLC. The expression of estrogen receptors β2 and IL-12Rβ2 was confirmed by Western blot and RT-PCR analysis in frozen tissues. The correlation between their expression levels and clinical characteristics was evaluated by Mann-Whitney and Kruskal-Wallis test. Using Kaplan-Meier plots and Cox proportional hazard models analyses, overall survival (OS) was evaluated. In contrast to benign pulmonary, ERβ2 and IL-12Rβ2 were over-expressed in NSCLC (p = 0.000). IHC results showed significant correlation between ERβ2 and IL-12Rβ2 (R = 0.382, p = 0.005). By analyzing the relation between ERβ2, IL-12Rβ2 mRNA expression levels and clinical characteristics, it was revealed that ERβ2 and IL-12Rβ2 were significant correlated with regional lymph node metastasis, T stage and clinical stage (p = 0.000/0.000; 0.001/0.000; 0.031/0.003 respectively), and both protein expression levels were lower with TNM stage being higher. In a Kaplan-Meier analysis, compared to both ERβ2 and IL-12Rβ2 or one low expression, high expression levels of ERβ2 and IL-12Rβ2 were identified in a group of patients with the longest overall survival (OS). Cox proportional hazard models revealed that ERβ2 and IL-12Rβ5 had longer OS. This is the first study to uncover that both ERβ2 and IL-12Rβ2 were over-expressed and further show that they were co-expressed in NSCLC. Moreover, we found that high expression levels of ERβ2 and IL-12Rβ2 may be positively correlated with OS and have prognostic values for the progression of NSCLC.

show abstract

Estrogen Receptors Β — New Target in Cellular Lung Cancer Treatment

Abstract: Обзор данных литературы об экспрессии разных типов эстрогеновых рецепторов (ЭРα иЭРβ

Cited by 8 publications

References 36 publications

Estrogen and insulin‐like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice

Estrogen and insulin‐like growth factor 1 synergistically promote the development of lung adenocarcinoma in mice

Fulvestrant-Mediated Inhibition of Estrogen Receptor Signaling Slows Lung Cancer Progression

The co-expression of ERβ2 and IL-12Rβ2 is better prognostic factor in non-small-cell lung cancer progression

Contact Info

Product

Resources

About