Estrogen receptor alpha promotes smoking-carcinogen-induced lung carcinogenesis via cytochrome P450 1B1

Li, Ming Yue; Liu, Yi; Liu, Li Zhong; Kong, Angel Wing-Yan; Zhao, Zhili; Wu, Bin; Long, Xiang; Wu, Jun; Ng, Calvin S. H.; Wan, Innes Y.P.; Du, Jing; Mok, Tony; Underwood, Malcolm J.; Chen, George G.

doi:10.1007/s00109-015-1300-4

Cited by 12 publications

(11 citation statements)

References 43 publications

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“…Moreover, CS was found to accelerate the production of the carcinogenic estrogenic metabolites 4-OHEs in the lungs (76), and the role that estrogen-metabolizing enzymes such as Cytochrome P450 1b1 (CYP1B1) may have in the enhanced female genderrelated susceptibility to tobacco has also been previously reported (75,81,82). The CS carcinogen nicotine-derived nitrosamine ketone (NNK) was shown to induce ERα via CYP1B1 activation (83), and anti-estrogens effectively inhibited NNK-induced murine lung carcinogenesis (84).…”

Section: Sex Differences In Lc Susceptibilitymentioning

confidence: 83%

A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer

Cohen

Burgos-Aceves²,

Smith³

2016

Transl. Lung Cancer Res.

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Alteration in the expression of microRNAs (miRNAs) is associated with oncogenesis and cancer progression. In this review we aim to suggest that elevated levels of estrogens and their metabolites inside the lungs as a result of cigarette smoke exposure can cause widespread repression of miRNA and contribute to lung tumor development. Anti-estrogenic compounds, such as the components of cruciferous vegetables, can attenuate this effect and potentially reduce the risk of lung cancer (LC) among smokers. (Table 1), and seem to work differently depending on the cellular context (47). However, developing any type of LC by deregulation of miRNAs via ER-Estrogen effect is still not entirely clear (8). miRNAs repression by cigarette smoke in the lungsWe have summarized before the results showing reduced expression levels of miRNAs in various tumors and cancer cell lines, including LC (48). The observation of a global miRNA repression in the lungs of rodents exposed to CS has also been reported (49)(50)(51)(52). Izzotti et al. show in their results the extensive down-regulation of 126 miRNAs in lungs of rats, 4 weeks after CS exposure (49). Such a short-lasting exposure to CS resulted in reversible miRNA alterations, as miRNA down-regulation was considerably attenuated one week after smoking cessation (51). By contrast, the repression of miRNA detected in mice exposed to CS for 4 months still persisted 3 months after smoking cessation, with the progressive development of cancer in the lung, suggesting that long-lasting exposure is needed to induce irreversible miRNA alterations (51,53). In their previous published results, using the same animal model, Izzotti et al. have found that CS up-regulates gene transcription and protein expression (54,55). The authors suggested that the CS-induced down-regulation of miRNA cause oncogene activation and cell proliferation, and that the persistence of these molecular alterations is crucial to commit lung cells towards carcinogenesis (51,53). These results are supported by the study of Schembri et al., who found that most of the differentially expressed miRNAs in the human bronchial airway epithelium were downregulated in smokers and were inversely correlated with their predicted targets (56). The same phenomenon was also observed in alveolar macrophages of smokers, where CS decreased global miRNA expression, while increased their predicted targets (57). In this later study the decrease in global miRNA expression was more pronounced in heavy smokers, suggesting that the magnitude of miRNA repression is related to the extent of smoking history (57). Anti-estrogenic compounds as attenuators of cigarette smoke effectsStudies suggest that phytochemicals from vegetables and fruits exhibit chemopreventive activities against various types of cancer (58). Izzotti et al. (59) evaluated miRNA expression in the lungs of rats exposed to CS and treated with several cancer chemopreventive agents. Administration of the dietary agents, Phenethyl isothiocyanate (PEITC) and Indole-3-carbi...

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Section: Sex Differences In Lc Susceptibilitymentioning

confidence: 83%

A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer

Cohen

Burgos-Aceves²,

Smith³

2016

Transl. Lung Cancer Res.

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“…From this table, three important conclusions are obtained. First, those genes found in the literature as biomarkers such as CYPIB1 and FABP4 validate our method. Secondly, those genes found in the literature as associated with other types of cancer, such as, XIST (a nonprotein coding gene) , among others, could eventually be validated and proposed as lung cancer biomarkers with the precursor that they are important genes for other types of cancer and could uncover relations between different cancer types.…”

Section: Discussionmentioning

confidence: 64%

Multiple criteria optimization joint analyses of microarray experiments in lung cancer: from existing microarray data to new knowledge

et al. 2015

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Microarrays can provide large amounts of data for genetic relative expression in illnesses of interest such as cancer in short time. These data, however, are stored and often times abandoned when new experimental technologies arrive. This work reexamines lung cancer microarray data with a novel multiple criteria optimization‐based strategy aiming to detect highly differentially expressed genes. This strategy does not require any adjustment of parameters by the user and is capable to handle multiple and incommensurate units across microarrays. In the analysis, groups of samples from patients with distinct smoking habits (never smoker, current smoker) and different gender are contrasted to elicit sets of highly differentially expressed genes, several of which are already associated to lung cancer and other types of cancer. The list of genes is provided with a discussion of their role in cancer, as well as the possible research directions for each of them.

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“…Clinically, the over-expression of ERα is associated with a poor prognosis in lung adenocarcinoma patients both for men and women [10, 29-31]. In animal model, enhanced E2/ERα facilitates the smoking carcinogen N-nitrosamines-mediated lung carcinogenesis [32]. We demonstrated here an association between Orai3 expression and tobacco exposure.…”

Section: Discussionmentioning

confidence: 66%

Orai3 is a predictive marker of metastasis and survival in resectable lung adenocarcinoma

et al. 2016

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Orai3 channel has emerged as important player in malignant transformation. Indeed, its expression is increased in cancer and favors cell proliferation and survival by permitting calcium influx. In this study, Orai3 was overexpressed in lung adenocarcinoma as compared to their matched non-tumour samples and was associated with tumoural aggressiveness. Moreover, its expression was associated with estrogen receptor alpha (ERα) expression and visceral pleural invasion in multivariate analysis. Furthermore, both the overall survival (OS) median and the metastasis free survival (MFS) median of tumors with high Orai3 expression were lower than in low Orai3 expression regardless of cancer stage (35.01 months vs. 51.11 months for OS and 46.01 months vs. 62.04 months for MFS). In conclusion, Orai3 protein level constitutes an independent prognostic marker in lung adenocarcinoma, and a novel prognostic marker that could help selecting the patients with worst prognosis to be treated with adjuvant chemotherapy in resectable stage.

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Estrogen receptor alpha promotes smoking-carcinogen-induced lung carcinogenesis via cytochrome P450 1B1

Abstract: 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.

Cited by 12 publications

References 43 publications

A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer

A potential role for estrogen in cigarette smoke-induced microRNA alterations and lung cancer

Multiple criteria optimization joint analyses of microarray experiments in lung cancer: from existing microarray data to new knowledge

Orai3 is a predictive marker of metastasis and survival in resectable lung adenocarcinoma

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