Dynamic changes in DNA methylation during multistep rat lung carcinogenesis induced by 3-methylcholanthrene and diethylnitrosamine

Liu, Wenbin; Liu, Jinyi; Ao, Lin; Zhou, Ziyuan; Zhou, Yanhong; Cui, Zhihong; Yang, Huan; Cao, Jia

doi:10.1016/j.toxlet.2009.04.022

Cited by 32 publications

(33 citation statements)

References 41 publications

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“…CDKN2A/B are tumor suppressors and their expression might be upregulated in cellular senescence, and remarkably in the ageing process (Collado, Blasco & Serrano, ). The activity of CDKN2A finally leads to preventing cancer, and might promote aging (Liu, ). Uncontrolled cell proliferation due to loss of CDKN2A function by deletion, a point mutation, or promoter methylation might lead to neoplastic transformation, which has been reported in various cancers (Nosho et al, ; Samowitz et al, ).…”

Section: Discussionmentioning

confidence: 99%

Association of cyclin‐dependent kinase inhibitor 2A/B with increased risk of developing breast cancer

Seifi

Pouya

Rahmani

et al. 2019

Journal Cellular Physiology

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There is a growing body of data reporting the association of genetic alterations in chromosome 9P21 with the risk of developing cancer. In the current study, we studied the association of a genetic variant in CDKN2A/B, rs1333049, with the risk of developing breast cancer. A total of 339 participants with and without breast cancer entered to the study. Genotyping was done by the TaqMan real‐time polymerase chain reaction (RT‐PCR) method and gene expression analysis was ran by RT‐PCR. Our data showed that the minor allele homozygote in the total population was 10%, whereas for heterozygote was 38%. The dominant genetic model demonstrated that individuals with breast cancer had advanced TNM classification. Moreover, the logistic regression revealed that individuals who had CC/CG genotypes might have an enhanced risk of developing breast cancer when compared to the holders of GG genotype (e.g., OR = 2.8; 95% CI,1.4–5.4; p = .001), after regulated for confounders; age and body mass index. Furthermore, our analysis showed that the CDKN2A/B gene was downregulated in patients (p < .001). We showed a meaningful relationship of CDKN2A/B with the risk of breast cancer, cancer, showing the importance of studies in great sample size and several centers for studying the value of the marker as a risk classification in the management of patients with breast cancer.

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Section: Discussionmentioning

confidence: 99%

Association of cyclin‐dependent kinase inhibitor 2A/B with increased risk of developing breast cancer

Seifi

Pouya

Rahmani

et al. 2019

Journal Cellular Physiology

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“…Several lines of evidence support the hypothesis that epigenetic changes represented as CpG island methylation associated with tumor‐related gene silencing play an important role during carcinogenesis . To identify additional methylation sites for early diagnosis and therapeutic targets in lung cancer, we screened many novel differentially hyper/hypomethylated genomic regions in rat and human lung cancer tissues compared to those in normal lung tissues . Here, related regulation mechanism and functional studies defined a role of the CpG island region of ALX4 in lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Primer pairs that specifically amplified either methylated or unmethylated sequences spanning the CpG island of human ALX4 were used for MSP (Supporting Information Table 1). PCR conditions for MSP of ALX4 have been standardized in our laboratory . Normal blood genomic DNA untreated and treated with SssI methylase (New England Biolabs, Beverly, MA) was used as fully methylated and fully unmethylated controls in all PCRs, respectively.…”

Section: Methodsmentioning

confidence: 99%

Epigenetic silencing of Aristaless‐like homeobox‐4, a potential tumor suppressor gene associated with lung cancer

Liu

Han

et al. 2013

Intl Journal of Cancer

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Using genome-wide methylation screening, we found Aristaless-like homeobox-4 (ALX4) preferentially methylated in lung cancer. ALX4 is a putative transcription factor that belongs to the family of paired-class homeoproteins involved in epithelial development. However, the role of ALX4 in tumorigenesis remains largely unclear. Here, we analyzed its epigenetic regulation, biological functions and related molecular mechanisms in lung cancer. CpG island methylation and expression of ALX4 were evaluated by methylation-specific polymerase chain reaction (PCR), bisulfite genomic sequencing, reverse-transcription PCR and Western blotting. ALX4 functions were determined by cell viability, colony formation, flow cytometry and in vivo tumorigenicity assays. ALX4 hypermethylation was detected in 55% (54=98) of primary lung cancers compared to none (0=20) of the normal lung tissue samples tested (p < 0.01). ALX4 was readily expressed in normal lung tissues with an unmethylated status, but downregulated or silenced in 90% (9=10) of lung cancer cell lines with a hypermethylation status. Demethylation experiments further confirmed that loss of ALX4 expression was regulated by CpG island hypermethylation. Re-expression of ALX4 in lung cancer cell lines suppressed cell viability, colony formation and migration, whereas it induced apoptosis and G1=S arrest and restrained the tumorigenicity in nude mice. These effects were associated with upregulation of proapoptotic proteins caspase-7, -8 and -9, and downregulation of Bcl-2. On the other hand, knockdown of ALX4 expression by siRNA increased cell viability and proliferation, whereas it inhibited apoptosis and cell cycle arrest. In conclusion, our results suggest that ALX4 is a novel putative tumor suppressor with epigenetic silencing in lung carcinogenesis.

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“…Correspondingly, there is evidence that DNA methylation and other epigenetic changes in DNA increase with aging [82], and likely contribute to the pathogenesis of diseases such as diabetes and neurodegeneration [82,83]. Moreover, there is experimental evidence that nitrosamines, as well as other adduct forming toxins that contaminate foods, can mediate DNA methylation [84,85]. Since it could take years for epigenetic modifications to cause disease, and the findings in the "Nun Study" suggest that early events in life predispose individuals to develop AD [53], we utilized an experimental animal model in which low-dose NDEA exposures were administered early in life.…”

Section: Discussionmentioning

confidence: 99%

Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

Monte

Tong

Lawton

et al. 2009

Molecular Neurodegeneration

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Background: The current epidemics of type 2 diabetes mellitus (T2DM), non-alcoholic steatohepatitis (NASH), and Alzheimer's disease (AD) all represent insulin-resistance diseases. Previous studies linked insulin resistance diseases to high fat diets or exposure to streptozotocin, a nitrosamine-related compound that causes T2DM, NASH, and AD-type neurodegeneration. We hypothesize that low-level exposure to nitrosamines that are widely present in processed foods, amplifies the deleterious effects of high fat intake in promoting T2DM, NASH, and neurodegeneration.

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Dynamic changes in DNA methylation during multistep rat lung carcinogenesis induced by 3-methylcholanthrene and diethylnitrosamine

Cited by 32 publications

References 41 publications

Association of cyclin‐dependent kinase inhibitor 2A/B with increased risk of developing breast cancer

Association of cyclin‐dependent kinase inhibitor 2A/B with increased risk of developing breast cancer

Epigenetic silencing of Aristaless‐like homeobox‐4, a potential tumor suppressor gene associated with lung cancer

Nitrosamine exposure exacerbates high fat diet-mediated type 2 diabetes mellitus, non-alcoholic steatohepatitis, and neurodegeneration with cognitive impairment

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