Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer

Minna, John D.

doi:10.1172/jci17492

Cited by 95 publications

(86 citation statements)

References 26 publications

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“…Nicotine is being used widely to aid smoking cessation (1,2), yet nicotine use has been associated with lung tumorigenesis (12)(13)(14)16). Studies have demonstrated that transient nicotine exposure promotes lung epithelial cell survival by activating various intracellular growth factors, such as PKC, or by upregulating Bcl-2 activity to antagonize apoptotic signals (16).…”

Section: Discussionmentioning

confidence: 99%

“…Studies have demonstrated that transient nicotine exposure promotes lung epithelial cell survival by activating various intracellular growth factors, such as PKC, or by upregulating Bcl-2 activity to antagonize apoptotic signals (16). Other studies show, in vitro and in vivo, that nicotine stimulates angiogenesis in the settings of inflammation, ischemia, atherosclerosis, and tumor growth (3,4).…”

Section: Discussionmentioning

confidence: 99%

“…The activities of MAP kinase and extracellular signal-regulated kinase 1/2 were also elicited by nicotine. The activation of these kinases is responsible for the phosphorylation of Bcl-2, which blocks apoptosis in lung cancer cells (9,13,15,16). Using short-term cultures of normal human or murine bronchial epithelial cells or airway epithelial cells, studies show that nicotine is able to induce the activation of Akt.…”

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confidence: 99%

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Long-term Exposure to Nicotine, via Ras Pathway, Induces Cyclin D1 to Stimulate G1 Cell Cycle Transition

Chu

Guo

Chen

2005

Journal of Biological Chemistry

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Nicotine, a major component in tobacco, has been implicated as a potential factor that promotes the development of lung cancer. However, the molecular mechanism of its action is still unclear. In this study, we have shown that, via nicotinic acetylcholine receptors, persistent exposure of mouse epithelial cells to nicotine elicits Ras signaling and subsequent Raf/MAP kinase activity, accompanied by a significant increase in cyclin D1 promoter activity and its protein expression. AP-1 is required for activation of the cyclin D1 promoter. The induction of cyclin D1 expression and its promoter activity by nicotine is abolished by the suppression of Raf/MAP kinase signaling. Furthermore, upon nicotine treatment, the cells do not arrest in the G 1 phase of the cell cycle following serum starvation. The perturbation of the G 1 cell cycle checkpoint is caused by the deregulation of retinoblastoma/E2F activity. Therefore, our data indicated that by targeting the Ras pathway, longterm exposure to nicotine disrupts cell cycle restriction machinery and thus potentiates tumor development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Long-term Exposure to Nicotine, via Ras Pathway, Induces Cyclin D1 to Stimulate G1 Cell Cycle Transition

Chu

Guo

Chen

2005

Journal of Biological Chemistry

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“…In addition to the mutagenic effect of tobacco-specific nitrosamines like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and NЈ-nitrosonornicotine (NNN), these agents and nicotine can affect cellular functions through nicotinic acetylcholine receptors (nAChRs) (51,52,65). While nAChRs are mainly expressed in neurons and neuromuscular junctions, they are also present on a variety of nonneuronal cells, where they induce cell proliferation, invasion, and angiogenesis (16,19,20,36,53,67). While there is scant evidence that nicotine contributes to the initiation of tumors, it has been demonstrated that nicotine can promote the growth and metastasis of solid tumors in vivo (10,44), suggesting that nicotine might be promoting the progression of tumors already initiated by the tobacco-specific nitrosamines (10).…”

mentioning

confidence: 99%

ID1 Facilitates the Growth and Metastasis of Non-Small Cell Lung Cancer in Response to Nicotinic Acetylcholine Receptor and Epidermal Growth Factor Receptor Signaling

Pillai

Rizwani

et al. 2011

Molecular and Cellular Biology

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“…Indeed, they are expressed in the core region of the brain that is closely related to nicotine addiction (10,16). Receptors distributed in lung epithelial cells are involved in signal transduction of nicotine and tobacco carcinogens and can promote cell proliferation and metastasis of cancer cells (17)(18)(19). Previous research on two of the genes in this family, CHRNA5 and CHRNA3, demonstrated associations of polymorphisms in these genes with lung cancer susceptibility in smokers (9).…”

Section: Discussionmentioning

confidence: 99%

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

Shen¹,

Zhu²,

Zheng³

et al. 2013

Braz. J. Med. Biol. Res.

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Polymorphisms in the nicotinic acetylcholine receptor subunit CHRNA5 gene have been associated with lung cancer positive susceptibility in European and American populations. In the present hospital-based, case-control study, we determined whether polymorphism in rs503464 of CHRNA5 is associated with lung cancer risk in Chinese individuals. A single nucleotide polymorphism in CHRNA5 rs503464, c.-166T.A (hereafter T.A), was identified using TaqMan-MGB probes with sequencing via PCR in 600 lung cancer cases and 600 healthy individuals. Genotype frequencies for rs503464 (T.A) were in HardyWeinberg equilibrium for the control population. However, genotype frequencies were significantly different between cases and controls (P , 0.05), while allele frequencies were not significantly different between groups. Compared to homozygous genotypes (TT or AA), the risk of lung cancer in those with the heterozygous genotype (TA) was significantly lower (OR = 0.611, 95%CI = 0.486-0.768, P = 0.001). Using genotype AA as a reference, the risk of lung cancer for those with genotype TA was increased 1.5 times (OR = 1.496, 95%CI = 1.120-1.997, P = 0.006). However, no difference in risk was observed between T allele carriers and A allele carriers (OR = 0.914, 95%CI = 0.779-1.073, P = 0.270). Stratification analysis showed that the protective effect of TA was more pronounced in those younger than 60 years, nonsmokers, or those without a family history of cancer, as well as in patients with adenocarcinoma or squamous cell carcinoma in clinical stages III or IV (P , 0.05). Therefore, the heterozygous genotype c.-166T.A at rs503464 of CHRNA5 may be associated with reduced risk of lung cancer, thus representing a susceptibility allele in Chinese individuals.

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Nicotine exposure and bronchial epithelial cell nicotinic acetylcholine receptor expression in the pathogenesis of lung cancer

Cited by 95 publications

References 26 publications

Long-term Exposure to Nicotine, via Ras Pathway, Induces Cyclin D1 to Stimulate G1 Cell Cycle Transition

Long-term Exposure to Nicotine, via Ras Pathway, Induces Cyclin D1 to Stimulate G1 Cell Cycle Transition

ID1 Facilitates the Growth and Metastasis of Non-Small Cell Lung Cancer in Response to Nicotinic Acetylcholine Receptor and Epidermal Growth Factor Receptor Signaling

CHRNA5 polymorphism and susceptibility to lung cancer in a Chinese population

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