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Estrogen, Estrogen Receptor and Lung Cancer.

ABSTRACT: Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER) in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR), and the relevant clinical trials combining the ER antagonist and the EGFR antagonist, to investigate the role of estrogen in lung cancer. Estrogen and its receptor have the potential to become a prognosticator and a therapeutic target in lung cancer. On the other hand, tobacco smoking aggravates the effect of estrogen and endocrine disruptive chemicals from the environment targeting ER may well contribute to the lung carcinogenesis. They have gradually become important issues in the course of preventive medicine.

SUBMITTER: Hsu LH

PROVIDER: S-EPMC5578103 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Estrogen, Estrogen Receptor and Lung Cancer.

Hsu Li-Han LH Chu Nei-Min NM Kao Shu-Huei SH

International journal of molecular sciences 20170805 8

Estrogen has been postulated as a contributor for lung cancer development and progression. We reviewed the current knowledge about the expression and prognostic implications of the estrogen receptors (ER) in lung cancer, the effect and signaling pathway of estrogen on lung cancer, the hormone replacement therapy and lung cancer risk and survival, the mechanistic relationship between the ER and the epidermal growth factor receptor (EGFR), and the relevant clinical trials combining the ER antagoni ...[more]

PMID: 28783064

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| S-EPMC2818690 | biostudies-literature

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| S-EPMC3557142 | biostudies-literature

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| S-EPMC4195686 | biostudies-literature

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| S-EPMC5459550 | biostudies-literature

Interaction between the estrogen receptor and fibroblast growth factor receptor pathways in non-small cell lung cancer.

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| S-EPMC5421827 | biostudies-literature

Progesterone and estrogen receptor expression and activity in human non-small cell lung cancer.

Project description:Lung cancer is the most common cause of cancer mortality in male and female patients in the US. Although it is clear that tobacco smoking is a major cause of lung cancer, about half of all women with lung cancer worldwide are never-smokers. Despite a declining smoking population, the incidence of non-small cell lung cancer (NSCLC), the predominant form of lung cancer, has reached epidemic proportions particularly in women. Emerging data suggest that factors other than tobacco, namely endogenous and exogenous female sex hormones, have a role in stimulating NSCLC progression. Aromatase, a key enzyme for estrogen biosynthesis, is expressed in NSCLC. Clinical data show that women with high levels of tumor aromatase (and high intratumoral estrogen) have worse survival than those with low aromatase. The present and previous studies also reveal significant expression and activity of estrogen receptors (ER?, ER?) in both extranuclear and nuclear sites in most NSCLC. We now report further on the expression of progesterone receptor (PR) transcripts and protein in NSCLC. PR transcripts were significantly lower in cancerous as compared to non-malignant tissue. Using immunohistochemistry, expression of PR was observed in the nucleus and/or extranuclear compartments in the majority of human tumor specimens examined. Combinations of estrogen and progestins administered in vitro cooperate in promoting tumor secretion of vascular endothelial growth factor and, consequently, support tumor-associated angiogenesis. Further, dual treatment with estradiol and progestin increased the numbers of putative tumor stem/progenitor cells. Thus, ER- and/or PR-targeted therapies may offer new approaches to manage NSCLC.

| S-EPMC3129425 | biostudies-literature

Comparison between Estrogen receptor positive and Estrogen receptor negative breast cancer samples

Project description:Comparison between Estrogen receptor positive and Estrogen receptor negative breast cancer samples Keywords: breast cancer type comparison 152 unique breast cancer tissue sample are included in the analysis. The total mRNA has been labeled with Cy5 and then hybridized on a two color arrays against the stratagen Human common reference that was previously labelled with Cy3.

| S-ECPF-GEOD-10510 | biostudies-other

Combined analysis of estrogen receptor beta-1 and progesterone receptor expression identifies lung cancer patients with poor outcome.

Project description:PurposeSteroid hormones and growth factors affect lung cancer, and it is possible they act in concert to influence patient outcome.Experimental designPrimary lung tumors and normal lung tissue were analyzed for expression and localization of estrogen receptor α and β-1 (ERα and ERβ), aromatase, progesterone receptor (PR), and epidermal growth factor receptor (EGFR).ResultsTumors expressed higher levels of ERβ compared to matched normal lung, whereas the reverse was true of PR. High cytoplasmic ERβ expression was identified as an independent negative prognostic predictor of overall survival (OS; HR = 1.67), and low total PR was identified as an independent negative predictor of time to progression (TTP; HR = 1.59). After adjusting for stage, age, sex, and smoking, combined high cytoplasmic ERβ and low total PR showed enhanced effects on OS (HR = 2.64) and on TTP (HR = 6.02). Further effects on OS were observed when EGFR expression was included (HR = 5.32). Patients with low cytoplasmic ERβ, low aromatase, low EGFR, and high total PR had shorter OS than patients with the opposite pattern (HR = 6.60). Contribution of these markers to survival showed no significant sex differences in a multivariable model. ERα was elevated in tumors but was not predictive of survival, and appears to represent a variant ERα protein that is only recognized by a C-terminal antibody.ConclusionsHormonal and EGFR pathways together may contribute to lung cancer prognosis. Lung tumors with high ERβ-1/low PR may define patients with aggressive biology. A validation study is necessary to fully assess the predictive value of these markers.

| S-EPMC3064257 | biostudies-literature

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