ArticleJournal of molecular medicine (Berlin, Germany)2015
Estrogen receptor alpha promotes smoking-carcinogen-induced lung carcinogenesis via cytochrome P450 1B1.
Article in Journal of molecular medicine (Berlin, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 2 of them syntheses that pooled it.
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Who cites it
7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- Construction of a 26‑feature gene support vector machine classifier for smoking and non‑smoking lung adenocarcinoma sample classification.Molecular medicine reports · 2018Pooled it
- Multiple criteria optimization joint analyses of microarray experiments in lung cancer: from existing microarray data to new knowledge.Cancer medicine · 2015Pooled it
- CMaf-Inducing Protein Promotes LUAD Proliferation and Metastasis by Activating the MAPK/ERK Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Identification of dynamic signatures associated with smoking-related squamous cell lung cancer and chronic obstructive pulmonary disease.Journal of cellular and molecular medicine · 2020Article
- EGFR-AS1/HIF2A regulates the expression of FOXP3 to impact the cancer stemness of smoking-related non-small cell lung cancer.Therapeutic advances in medical oncology · 2019Article
- Orai3 is a predictive marker of metastasis and survival in resectable lung adenocarcinoma.Oncotarget · 2016Article
- A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer.Translational lung cancer research · 2016Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledSmoking carcinogen N-nitrosamines such as 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) require metabolic activation to exert their genotoxicity. The first activation step is mainly catalyzed by cytochrome P450 (CYP) family. Estrogen receptor α (ERα) plays a role in lung pathology. The association between them is unknown. In this study, we explored the relationship and function of CYP1B1 and ERα in NNK-induced lung tumorigenesis. CYP1B1 and ERα expression was analyzed in human lung cancer tissues and NNK-induced lung tumor of A/J mice. Cell lines NCI-H23 and NCI-H460 were employed to further study the responsible mechanisms using various cellular and molecular approaches. Our in vivo experiments demonstrated that CYP1B1 and ERα were over-expressed at the early stage of NNK-induced lung tumorigenesis. Microarray analysis found that ERα was involved in the extracellular-signal-regulated kinase (ERK)/MAPK pathway. NNK activated RAS/ERK/AP1 as it remarkably increased the levels of p-ERK, c-Fos, and c-Jun but inhibited multiple negative regulators of Ras/ERK/AP1, Pdcd4, Spry1, Spry2, and Btg2 through up-regulating miR-21. Both CYP1B1 siRNA and ERK-specific inhibitor U0126 suppressed NNK-mediated ERα up-regulation, suggesting that ERα was downstream of CYP1B1 and ERK. ERK inactivation led to the accumulation of CYP1B1, indicating that CYP1B1 was upstream of ERK activation. Inhibition of ERK or ERα decreased NNK-induced cell proliferation. Blockage of CYP1B1 or ERα induced apoptosis of lung cancer cells. Collectively, NNK-mediated ERα induction is via CYP1B1 and ERK and contributes to the lung carcinogenesis. The inhibition of CYP1B1, ERK, or ERα may arrest the lung cancer cell growth, implicating a pivotal strategy for the treatment of lung cancer. KEY MESSAGES: Smoking carcinogen NNK requires metabolic activation to exert their genotoxicity. CYP1B1 is the enzyme to catalyze NNK. NNK activates CYP1B1 and ERK to induce ERα. Inhibition of CYP1B1, ERK, or ERα arrests the lung cancer cell growth.
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