Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis

Egleton, Richard D.; Brown, Kathleen C.; Dasgupta, Piyali

doi:10.1016/j.tips.2007.12.006

Cited by 250 publications

(246 citation statements)

References 54 publications

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“…50 On the contrary, many authors have noticed that ␣7 is the main nAChR subunit that mediates the proliferative effects of nicotine in cancer cell lines. 12 This ␣7 nAChR-mediated stimulatory effect of nicotine was also observed in commercialized normal bronchial epithelial cells, after these cells have been amplified after isolation. 51 At the opposite, we always observed a stimulatory proliferative action of ␣BTX on primary cultures of freshly isolated HAECs and on purified human airway basal cells.…”

Section: Discussionmentioning

confidence: 76%

“…[7][8][9] ␣7 nAChR is characterized by an elevated Ca 2ϩ permeability 10 and has been involved in several important biological processes such as cell proliferation, apoptosis, and angiogenesis in cancer. 11,12 Prenatal nicotine exposure significantly increases pulmonary ␣7 nAChR expression and alters fetal lung development 13 and subsequently pulmonary function in newborn. 14 In particular, alteration of lung branching morphogenesis induced by nicotine is mediated by ␣7 nAChR.…”

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confidence: 99%

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α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

Maouche

Polette

Jolly

et al. 2009

The American Journal of Pathology

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Airway epithelial basal cells are known to be critical for regenerating injured epithelium and maintaining tissue homeostasis. Recent evidence suggests that the ␣7 nicotinic acetylcholine receptor (nAChR), which is highly permeable to Ca 2؉ , is involved in lung morphogenesis. Here, we have investigated the potential role of the ␣7 nAChR in the regulation of airway epithelial basal cell proliferation and the differentiation of the human airway epithelium. In vivo during fetal development and in vitro during the regeneration of the human airway epithelium, ␣7 nAChR expression coincides with epithelium differentiation. Inactivating ␣7 nAChR function in vitro increases cell proliferation during the initial steps of the epithelium regeneration, leading to epithelial alterations such as basal cell hyperplasia and squamous metaplasia, remodeling observed in many bronchopulmonary diseases. The regeneration of the airway epithelium after injury in ␣7 The respiratory epithelium, which is constantly exposed to airborne pollutants, is frequently injured, which results in altered epithelial functions. To restore these functions, the respiratory epithelium must undergo rapid repair via epithelial cell spreading and migration and regenerate its structure via basal cell proliferation and differentiation.

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Section: Discussionmentioning

confidence: 76%

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confidence: 99%

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

Maouche

Polette

Jolly

et al. 2009

The American Journal of Pathology

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“…The subunits have been cloned from neuron-like cells or cDNA libraries obtained from vertebrate brain, but it has recently been shown that some of them are expressed by non-neuronal cell types throughout the body and have various functions. However, the nAChRs expressed in non-neuronal tissues are beyond the scope of this review and interested readers are referred elsewhere [17][18][19][20][21].…”

Section: Structure Of Thenachrmentioning

confidence: 99%

Structural and functional diversity of native brain neuronal nicotinic receptors

Gotti

Clementi

Fornari

et al. 2009

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Although some of the neural circuits involved in the acute and chronic effects of nicotine have been identified, much less is known about which native nAChR subtypes are involved in specific physiological functions and pathophysiological conditions.We briefly review some recent findings concerning the structure and function of native nAChRs, focusing on the subtypes identified in the meso-striatal and habenulo-interpeduncular pathways, two systems involved in nicotine reinforcement and withdrawal. We also discuss recent findings concerning the effect of chronic nicotine on the expression of native subtypes.

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“…The search for nicotine receptors linked to aberrant lung growth led to the discovery that nicotinic acetylcholine receptors (nAChRs) are significantly expressed in the non-neuronal tissues of the lung. 1 There are more than a dozen different nAChR subunit proteins, subdivided into ␣ and ␤ subfamilies, which form pentameric ion channels consisting of either a single type of ␣ subunit (homopentamers) or a combination of ␣ and ␤ subunits (heteropentamers).As ligand-gated ion channels, nAChRs undergo complex allosteric changes in response to binding either the endogenous ligand acetylcholine or exogenous ligands, including nicotine. Although nAChRs are classically linked to the plasma membrane depolarization required for neurotransmission, non-neuronal nAChRs in the lung act most frequently as calcium channels and have been linked to regulatory proteins such as src and phosphatidylinositol 3-kinase, which can control cell proliferation.…”

mentioning

confidence: 99%

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confidence: 99%

Control of Lung Epithelial Growth by a Nicotinic Acetylcholine Receptor

Roman

Koval

2009

The American Journal of Pathology

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Nicotine, a primary active component of tobacco, is a powerful stimulator of cell proliferation. The search for nicotine receptors linked to aberrant lung growth led to the discovery that nicotinic acetylcholine receptors (nAChRs) are significantly expressed in the non-neuronal tissues of the lung. 1 There are more than a dozen different nAChR subunit proteins, subdivided into ␣ and ␤ subfamilies, which form pentameric ion channels consisting of either a single type of ␣ subunit (homopentamers) or a combination of ␣ and ␤ subunits (heteropentamers).As ligand-gated ion channels, nAChRs undergo complex allosteric changes in response to binding either the endogenous ligand acetylcholine or exogenous ligands, including nicotine. Although nAChRs are classically linked to the plasma membrane depolarization required for neurotransmission, non-neuronal nAChRs in the lung act most frequently as calcium channels and have been linked to regulatory proteins such as src and phosphatidylinositol 3-kinase, which can control cell proliferation. 2 Moreover, although nAChR activation often leads to a positive feedback loop that induces receptor expression, chronic stimulation of nAChRs can lead to channel desensitization and decreased activity. Thus, elucidating functional roles for nAChRs is particularly complex and requires consideration of subunit composition, dose response, and duration of ligand stimulation.Although the majority of studies of nAChR function in the lung are related to the effects of nicotine on these receptors, little is known about the physiological functions of these receptors in regulating lung growth and repair. Emerging data show that airway epithelia secrete, process, reabsorb, and synthesize acetylcholine, underscoring a physiological role for nAChRs in normal lung function. 3 In this issue of The American Journal of Pathology, Maouche et al 4 used a multipronged approach to investigate roles for ␣7 nAChR, a widely expressed homopentamer, in regulating airway epithelial growth and differentiation.As a pseudostratified epithelium, the airway is composed of several phenotypically distinct cell types including ciliated cells, secretory cells, and basal cells, all in close proximity. By immunohistochemistry, Maouche et al found that basal cells, normally localized at the basement membrane, were enriched for ␣7 nAChR expression. Importantly, expression of ␣7 nAChRs was pronounced in proliferating cells in the developing lung. Given this and the more typical role for non-neuronal nAChRs in stimulating cell proliferation, it was interesting that functional experiments revealed a role for ␣7 nAChRs in limiting, not stimulating, basal cell proliferation. Specifically, the authors found that the injury response in airways of ␣7 nAChR-deficient mice was characterized by significant basal cell hyperplasia compared with wild-type mice. 4 Treatment of cultured human airway cells or ex vivo human lung explants with ␣-bungarotoxin, a neurotoxin capable of blocking ␣7 nAChR function, had a similar effect on the injury ...

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Nicotinic acetylcholine receptors in cancer: multiple roles in proliferation and inhibition of apoptosis

Cited by 250 publications

References 54 publications

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

Structural and functional diversity of native brain neuronal nicotinic receptors

Control of Lung Epithelial Growth by a Nicotinic Acetylcholine Receptor

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