p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients

Jha, Abhimanyu Kumar; Nikbakht, Mohsen; Jain, Veena; Capalash, Neena; Kaur, Jagdeep

doi:10.3892/ol.2012.655

Cited by 40 publications

(22 citation statements)

References 19 publications

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“…Significant promoter hypermethylation has been reported for both CDKN2A and CDKN2B in cervical cancer patients of North Indian origin (Jha et al 2012). …”

Section: Discussionmentioning

confidence: 99%

Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer

et al. 2014

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PurposeTo investigate the promoter methylation status at selected loci which encode for key proteins involved in apoptosis, DNA repair, cell cycle control and progression in urothelial cell carcinoma of bladder and compare the findings from tissue samples with that of plasma.MethodsTotal genomic DNA was isolated from 43 non-muscle invasive (low grade) and 33 muscle invasive (high grade) urothelial bladder cancer samples along with 10 control cases of normal bladder mucosa. Promoter methylation status was investigated for RASSF1A, APC, MGMT, CDKN2A and CDKN2B genes using real-time methylation-specific PCR with SYBR® green. Plasma samples from 16 patients with muscle invasive high grade bladder cancer were also subjected to similar analyses.ResultsPromoter hypermethylation was frequently observed in RASSF1A, APC and MGMT gene promoters (p-value < 0.001). The methylation was more prominent in the muscle invasive high grade bladder cancer when compared to non-muscle invasive low grade group (p-value < 0.001) and normal bladder mucosa (p-value < 0.05). The RNA expression of RASSF1A, APC and MGMT was also found to be decreased in the muscle-invasive high grade bladder cancer when compared to the non muscle invasive low grade group (p-value < 0.05). RASSF1A, MGMT and CDKN2A showed comparable results when data from 16 plasma samples was compared to the corresponding tissue samples.ConclusionOur results suggest that epigenetic silencing of RASSF1A, APC and MGMT genes is strongly associated with invasive high grade urothelial bladder cancer. Thus, status of promoter methylation has the potential to serve as valuable tool for assessing aggressiveness of urothelial cell carcinoma of bladder.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-178) contains supplementary material, which is available to authorized users.

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“…Significant promoter hypermethylation has been reported for both CDKN2A and CDKN2B in cervical cancer patients of North Indian origin (Jha et al 2012). …”

Section: Discussionmentioning

confidence: 99%

Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer

et al. 2014

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“…However, we have recently reported that curcumin can restore the expression of the Nrf2 and Neurog1 genes through DNA demethylation [57, 106]. Similarly, Jha et al demonstrated that curcumin can reverse CpG hypermethylation, leading to the activation of the RARβ2 gene in cervical cancer cell lines [211]. However, in another report, demethoxycurcumin and bisdemethoxycurcumin, but not curcumin, were found to be able to demethylate the WIF-1 promoter region in A549 cells [212].…”

Section: The Epigenomic Reactivation Of Nrf2 By Dietary Phytochemicalsmentioning

confidence: 99%

A Perspective on Dietary Phytochemicals and Cancer Chemoprevention: Oxidative Stress, Nrf2, and Epigenomics

Shu

Khor

et al. 2012

Topics in Current Chemistry

121

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Oxidative stress is caused by an imbalance of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and the antioxidative stress defense systems in cells. ROS/RNS or carcinogen metabolites can attack intracellular proteins, lipids, and nucleic acids, which can result in genetic mutations, carcinogenesis, and other diseases. Nrf2 plays a critical role in the regulation of many antioxidative stress/antioxidant and detoxification enzyme genes, such as glutathione Stransferases (GSTs), NAD(P)H:quinone oxidoreductase 1 (NQO1), UDP-glucuronyl transferases (UGTs), and heme oxygenase-1 (HO-1), directly via the antioxidant response element (ARE). Recently, many studies have shown that dietary phytochemicals possess cancer chemopreventive potential through the induction of Nrf2-mediated antioxidant/detoxification enzymes and antiinflammatory signaling pathways to protect organisms against cellular damage caused by oxidative stress. In addition, carcinogenesis can be caused by epigenetic alterations such as DNA methylation and histone modifications in tumor-suppressor genes and oncogenes. Interestingly, recent studies have shown that several naturally occurring dietary phytochemicals can epigenetically modify the chromatin, including reactivating Nrf2 via demethylation of CpG NIH Public Access islands and the inhibition of histone deacetylases (HDACs) and/or histone acetyltransferases (HATs). The advancement and development of dietary phytochemicals in cancer chemoprevention research requires the integration of the known, and as-yet-unknown, compounds with the Nrf2-mediated antioxidant, detoxification, and anti-inflammatory systems and their in vitro and in vivo epigenetic mechanisms; human clinical efficacy studies must also be performed.

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“…Deletion of p15 INK4b gene was found in 21.4% of cases (Eissa et al, 2000). Promoter methylation of the p15 INK4b gene, is involved in the pathogenesis of many different types of cancer (Guo et Jha et al, 2012) To our knowledge, this is the first study to investigate the association between the expression of p15 INK4b In addition, the relationship between clinicopathologic variables of the patients (based on tissue cores) and p15 INK4b protein were analyzed. However, there were no significant relationship between the clinicopathologic variables and p15 INK4b expression.…”

Section: Discussionmentioning

confidence: 99%

Lack of Increased P15^INK4BProtein Expression in Basal Cell Carcinomas

Moad

Tan

Kaur

et al. 2012

Asian Pacific Journal of Cancer Prevention

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p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients

Cited by 40 publications

References 19 publications

Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer

Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer

A Perspective on Dietary Phytochemicals and Cancer Chemoprevention: Oxidative Stress, Nrf2, and Epigenomics

Lack of Increased P15^INK4BProtein Expression in Basal Cell Carcinomas

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p16INK4a and p15INK4b gene promoter methylation in cervical cancer patients

Cited by 40 publications

References 19 publications

Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer

Promoter hypermethylation of tumor suppressor genes correlates with tumor grade and invasiveness in patients with urothelial bladder cancer

A Perspective on Dietary Phytochemicals and Cancer Chemoprevention: Oxidative Stress, Nrf2, and Epigenomics

Lack of Increased P15INK4BProtein Expression in Basal Cell Carcinomas

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Lack of Increased P15^INK4BProtein Expression in Basal Cell Carcinomas