Estrogenic Steroid Hormones in Lung Cancer

Siegfried, Jill M.; Stabile, Laura P.

doi:10.1053/j.seminoncol.2013.12.009

Cited by 91 publications

(78 citation statements)

References 77 publications

(104 reference statements)

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“…The presence of receptors for both estrogen (ER α, ER β and GPER) and progesterone in lung cells 29, 30 , the pulmonary physiologic abnormalities associated with the targeted inactivation of ER β receptors in female mice 31 , the ER β receptor most often expressed in human non-small cell lung cancer cell lines and in normal pulmonary tissue of sick patients 30 , illustrate the plausibility of the role of steroid hormones in lung carcinogenesis. Furthermore, some studies have indicated differences in the expression of ERs depending on the sex of the subject and the cancer histology 10 .…”

Section: Discussionmentioning

confidence: 99%

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Menstrual and reproductive factors and lung cancer risk: A pooled analysis from the international lung cancer consortium

Khedher

Neri

Papadopoulos

et al. 2017

Intl Journal of Cancer

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Many clinical features of lung cancer are different in women and men. Sex steroid hormones exert effects in non-reproductive organs, such as the lungs. The association between menstrual and childbearing factors and the risk of lung cancer among women is still debated. We performed a pooled analysis of eight studies contributing to the International Lung Cancer Consortium (ILCCO; 4,386 cases and 4,177 controls). Pooled associations between menstrual or reproductive factors and lung cancer were estimated using multivariable unconditional logistic regression. Subgroup analyses were done for menopause status, smoking habits and histology. We found no strong support for an association of age at menarche and at menopause with lung cancer, but peri/postmenopausal women were at higher risk compared to premenopausal (OR 1.47, 95% CI 1.11–1.93). Premenopausal women showed increased risks associated with parity (OR 1.74, 95% CI 1.03–2.93) and number of children (OR 2.88 95% CI 1.21–6.93 for more than 3 children; P for trend 0.01) and decreased with breastfeeding (OR 0.54, 95% CI 0.30–0.98). In contrast, peri/postmenopausal subjects had ORs around unity for the same exposures. No major effect modification was exerted by smoking status or cancer histology. Menstrual and reproductive factors may play a role in the genesis of lung cancer, yet the mechanisms are unclear, and smoking remains the most important modifiable risk factor. More investigations in large well-designed studies are needed to confirm these findings and to clarify the underlying mechanisms of gender differences in lung cancer risk.

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Section: Discussionmentioning

confidence: 99%

“…Most studies have focused on estrogen receptors (ER α and ER β), but some evidence exists also for progesterone and androgen receptors. Local metabolism of sex steroids may also be important, as suggested by the presence of sex steroids synthesising enzymes in lung parenchyma 9, 10 .…”

Section: Introductionmentioning

confidence: 99%

Menstrual and reproductive factors and lung cancer risk: A pooled analysis from the international lung cancer consortium

Khedher

Neri

Papadopoulos

et al. 2017

Intl Journal of Cancer

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“…Results of studies from ER␣-negative/progesterone receptor-negative (ER␣ -/PR -) MDA-MB-453 and MDA-MB-468 breast cancer cell lines found that ER␤ can increase proliferation and survival suggesting that estrogen dependent activation of ER␤ in the absence of overriding effects of ER␣ may promote tumor growth (45). Although there are relatively few studies examining the role of ER␤ in tumors like Med that typically lack ER␣, lung cancer stands as an example of another nonreproductive estrogen responsive cancer that expresses ER␤ and not ER␣ (63). Similar to Med, in human lung cancers, ER␤ and IGF1R expression levels are positively correlated, and increased levels of their expression are associated with poor prognosis (64).…”

Section: Discussionmentioning

confidence: 99%

Estrogen Receptor-β Up-Regulates IGF1R Expression and Activity to Inhibit Apoptosis and Increase Growth of Medulloblastoma

Cookman

Belcher

2015

Endocrinology

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Medulloblastoma (Med) is the most common malignant brain tumor in children. The role of ESR2 [estrogen receptor (ER)-β] in promoting Med growth was comprehensively examined in three in vivo models and human cell lines. In a novel Med ERβ-null knockout model developed by crossing Esr2(-/-) mice with cerebellar granule cell precursor specific Ptch1 conditional knockout mice, the tumor growth rate was significantly decreased in males and females. The absence of Esr2 resulted in increased apoptosis, decreased B-cell lymphoma 2 (BCL2), and IGF-1 receptor (IGF1R) expression, and decreased levels of active MAPKs (ERK1/2) and protein kinase B (AKT). Treatment of Med in Ptch1(+/-) Trp53(-/-) mice with the antiestrogen chemotherapeutic drug Faslodex significantly increased symptom-free survival, which was associated with increased apoptosis and decreased BCL2 and IGF1R expression and signaling. Similar effects were also observed in nude mice bearing D283Med xenografts. In vitro studies in human D283Med cells metabolically stressed by glutamine withdrawal found that 17β-estradiol and the ERβ selective agonist 2,3-bis(4-hydroxyphenyl)-propionitrile dose dependently protected Med cells from caspase-3-dependent cell death. Those effects were associated with increased phosphorylation of IGF1R, long-term increases in ERK1/2 and AKT signaling, and increased expression of IGF-1, IGF1R, and BCL2. Results of pharmacological experiments revealed that the cytoprotective actions of estradiol were dependent on ERβ and IGF1R receptor tyrosine kinase activity and independent of ERα and G protein-coupled estrogen receptor 1 (G protein coupled receptor 30). The presented results demonstrate that estrogen promotes Med growth through ERβ-mediated increases in IGF1R expression and activity, which induce cytoprotective mechanisms that decrease apoptosis.

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“…There is concerted interest in the role ofhormone therapy influence on steroid receptor function in mediating the development and progression of many common cancers including those of the breast, endometrium, ovary, colon and rectum, and lung (1, 2, 3, 4). Relevant findings on this issue, with emphasis on randomized clinical trial findings, follows.…”

mentioning

confidence: 99%

Menopausal hormone therapy and cancer: Changing clinical observations of target site specificity

Chlebowski

Anderson

2014

Steroids

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Menopausal hormone therapy with estrogen plus progestin or estrogen alone (for women with prior hysterectomy) is still used by millions of women for climacteric symptom management throughout the world. Until 2002, hormone therapy influence on cancer risk and other chronic diseases was determined through observational study reports. Since then, results from the Women's Health Initiative randomized, placebo-controlled hormone therapy trials have substantially changed concepts regarding estrogen plus progestin and estrogen alone influence on the most common cancers in postmenopausal women. In these trials, estrogen plus progestin significantly increased breast cancer incidence and deaths from breast cancer, significantly increased deaths from lung cancer, significantly decreased endometrial cancer, and did not have a clinically significant influence on colorectal cancer. In contrast, estrogen alone use in women with prior hysterectomy significantly reduced breast cancer incidence and deaths from breast cancer without significant influence on colorectal cancer or lung cancer. These complex results are discussed in the context of known potential mediating mechanisms of action involved in interactionwith steroid hormone receptors.

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Estrogenic Steroid Hormones in Lung Cancer

Cited by 91 publications

References 77 publications

Menstrual and reproductive factors and lung cancer risk: A pooled analysis from the international lung cancer consortium

Menstrual and reproductive factors and lung cancer risk: A pooled analysis from the international lung cancer consortium

Estrogen Receptor-β Up-Regulates IGF1R Expression and Activity to Inhibit Apoptosis and Increase Growth of Medulloblastoma

Menopausal hormone therapy and cancer: Changing clinical observations of target site specificity

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