Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues

Wang, Rui; An, Jing; Ji, Fengqing; Jiao, Huiqin; Sun, Hongxia; Zhou, Dujin

doi:10.1016/j.bbrc.2008.06.004

Cited by 237 publications

(196 citation statements)

References 21 publications

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“…These proteins are responsible for purines synthesis, which are the building blocks of DNA and RNA, which in turn, leads to the proliferation of cancer cells (Mitsuishi et al 2012). Several studies have shown that elevated levels of Nrf2 in cancer cells are less sensitive to chemotherapeutic treatments and renders more resistant to cancer cells against a variety of anti-cancer agents (Shibata et al 2008a, b;Wang et al 2008). Several mechanisms are shown in behaviour following elevated levels of Nrf2 in cancer cells, which includes: (a) somatic mutation: gain-of-function mutations in Nrf2 and lossof-function mutations in Keap1 and CUL3 have been identified in several human cancers.…”

Section: Role Of the Nrf2-keap1 Pathway In Cancermentioning

confidence: 99%

“…Methylation in the promoter region of Keap1 affects its expression and hinders the ability to bind to the Nrf2. Therefore, this leads to the expression of Nrf2 (Wang et al 2008;Muscarella et al 2011). Conversely, DNA methylation by DNA methyltransferases (DNMTs) appears to downregulate the Nrf2 expression indirectly (Khor et al 2014;Yu et al 2010;Rajabi et al 2016;Tagde et al 2016b).…”

Section: Role Of the Nrf2-keap1 Pathway In Cancermentioning

confidence: 99%

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The Keap1–Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases

et al. 2016

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The overproduction of reactive oxygen species (ROS) generates oxidative stress in cells. Oxidative stress results in various pathophysiological conditions, especially cancers and neurodegenerative diseases (NDD). The Keap1-Nrf2 [Kelch-like ECH-associated protein 1-nuclear factor (erythroid-derived 2)-like 2] regulatory pathway plays a central role in protecting cells against oxidative and xenobiotic stresses. The Nrf2 transcription factor activates the transcription of several cytoprotective genes that have been implicated in protection from cancer and NDD. The Keap1-Nrf2 system acts as a double-edged sword: Nrf2 activity protects cells and makes the cell resistant to oxidative and electrophilic stresses, whereas elevated Nrf2 activity helps in cancer cell survival and proliferation. Several groups in the recent past, from both academics and industry, have reported the potential role of Nrf2-mediated transcription to protect from cancer and NDD, resulting from mechanisms involving xenobiotic and oxidative stress. It suggests that the Keap1-Nrf2 system is a potential therapeutic target to combat cancer and NDD by designing and developing modulators (inhibitors/activators) for Nrf2 activation. Herein, we review and discuss the recent advancement in the regulation of the Keap1-Nrf2 system, its role under physiological and pathophysiological conditions including cancer and NDD, and modulators design strategies for Nrf2 activation.

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Section: Role Of the Nrf2-keap1 Pathway In Cancermentioning

confidence: 99%

Section: Role Of the Nrf2-keap1 Pathway In Cancermentioning

confidence: 99%

The Keap1–Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases

et al. 2016

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“…We determined KEAP1 methylation levels in normal tissues and tumor specimens by using a primers/ probe set designed to amplify a CpG region showing the highest frequency of methylation and correlating with KEAP1 mRNA expression. 18,26,28 Methylation analysis was performed on DNA obtained from 6 normal breast tissues from reductive mammoplasty (NB), 14 pre-invasive lesions (PreINV), 102 invasive tumors (INV) along with 38 paired normal breast tissues distant from tumor (NBDT). Of the pre-invasive lesions, 12 were synchronous (9 DCIS and 3 ADH) to invasive cancer and 2 were only DCIS.…”

Section: Patients and Treatmentmentioning

confidence: 99%

AberrantKeap1methylation in breast cancer and association with clinicopathological features

et al. 2013

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“…In addition, because NFE2L2 activity is repressed by KEAP1, it is also conceivable that compensation occurs between these two central molecules via, e.g. epigenetic silencing of KEAP1 (Wang et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population

et al. 2011

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Air pollution and subsequent increased oxidative stress have long been recognized as contributing factors for asthma phenotypes. Individual susceptibility to oxidative stress is determined by genetic variations of the antioxidant defence system. In this study, we analysed the association between environmental nitrogen dioxide (NO 2 ) exposure and single nucleotide polymorphisms (SNP) in NFE2L2 and KEAP1 genes and their common impact on asthma risk.We genotyped 12 SNPs in a case-control study of 307 patients diagnosed with asthma and 344 controls. NO 2 concentration was collected from the period preceding the development of asthma symptoms. Multiple logistic regression was applied to evaluate the effects of the studied genetic variations on asthma outcomes in interaction with NO 2 exposure. Our data showed that genotypes of rs2588882 and rs6721961 in the regulatory regions of the NFE2L2 gene were inversely associated with infection-induced asthma (odds ratio (OR)00.290, p00.0015, and OR00.437, p0 0.007, respectively). Furthermore, case-only analyses revealed significant differences for these SNPs between asthma patients that lived in modestly or highly polluted environment , p 00.01, and OR 0 0.51, p00.02, respectively, in a dominant model). In conclusion, our results throw some new light upon the impact of NFE2L2 polymorphisms on infection-induced asthma risk and their effect in gene-environment interactions.

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Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues

Cited by 237 publications

References 21 publications

The Keap1–Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases

The Keap1–Nrf2 pathway: promising therapeutic target to counteract ROS-mediated damage in cancers and neurodegenerative diseases

AberrantKeap1methylation in breast cancer and association with clinicopathological features

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population

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