Epigenetics and prostate cancer: defining the timing of DNA methyltransferase deregulation during prostate cancer progression

Tzelepi, Vassiliki; Logotheti, Souzana; Efstathiou, Eleni; Troncoso, Patricia; Aparicio, Ana; Sakellakis, Minas; Hoang, Anh; Perimenis, Petros; Melachrinou, Maria; Logothetis, Christopher J.; Zolota, Vasiliki

doi:10.1016/j.pathol.2019.10.006

Cited by 29 publications

(39 citation statements)

References 56 publications

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“…Epigenetic perturbations have been increasingly documented in contributing to the initiation and progression of various cancers ( Kanwal et al, 2015 ) including stomach ( Samadani et al, 2019 ), lung ( Liu and Zhao, 2019 ), colon ( Jung et al, 2020 ), breast ( Pasculli et al, 2018 ), and prostate cancer ( Wu et al, 2015 ; Tzelepi et al, 2020 ). In general, one of the most recognized epigenetic changes in tumorigenesis is the methylation of genomic DNA at the 5 position of cytosine (5mC) ( Jones, 2012 ).…”

Section: Type 2 Inflammation-induced Epigenetic Changes May Underlie Autoimmune Tumorigenesismentioning

confidence: 99%

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Chen

2021

Front. Cell Dev. Biol.

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Recent epidemiological studies have found an alarming trend of increased cancer incidence in adults younger than 50 years of age and projected a substantial rise in cancer incidence over the next 10 years in this age group. This trend was exemplified in the incidence of non-cardia gastric cancer and its disproportionate impact on non-Hispanic white females under the age of 50. The trend is concurrent with the increasing incidence of autoimmune diseases in industrialized countries, suggesting a causal link between the two. While autoimmunity has been suspected to be a risk factor for some cancers, the exact mechanisms underlying the connection between autoimmunity and cancer remain unclear and are often controversial. The link has been attributed to several mediators such as immune suppression, infection, diet, environment, or, perhaps most plausibly, chronic inflammation because of its well-recognized role in tumorigenesis. In that regard, autoimmune conditions are common causes of chronic inflammation and may trigger repetitive cycles of antigen-specific cell damage, tissue regeneration, and wound healing. Illustrating the connection between autoimmune diseases and cancer are patients who have an increased risk of cancer development associated with genetically predisposed insufficiency of cytotoxic T lymphocyte-associated protein 4 (CTLA4), a prototypical immune checkpoint against autoimmunity and one of the main targets of cancer immune therapy. The tumorigenic process triggered by CTLA4 insufficiency has been shown in a mouse model to be dependent on the type 2 cytokines interleukin-4 (IL4) and interleukin-13 (IL13). In this type 2 inflammatory milieu, crosstalk with type 2 immune cells may initiate epigenetic reprogramming of epithelial cells, leading to a metaplastic differentiation and eventually malignant transformation even in the absence of classical oncogenic mutations. Those findings complement a large body of evidence for type 1, type 3, or other inflammatory mediators in inflammatory tumorigenesis. This review addresses the potential of autoimmunity as a causal factor for tumorigenesis, the underlying inflammatory mechanisms that may vary depending on host-environment variations, and implications to cancer prevention and immunotherapy.

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Section: Type 2 Inflammation-induced Epigenetic Changes May Underlie Autoimmune Tumorigenesismentioning

confidence: 99%

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Chen

2021

Front. Cell Dev. Biol.

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“…ROS increase the expression of DNA methyltransferases (DNMT) enzymes that either catalyze the transfer of a methyl group to DNA or speed up the reaction of DNA with the positive-charged intermediate S-adenosyl-L-methionine through deprotonating the cytosine molecule at the C-5 position in the process of DNA methylation [ 81 , 82 ]. Recent evidence shows that overexpression of DNMT plays critical roles in progression, metastases, and therapy resistance of PCa, particularly in advanced stage [ 83 , 84 ]. ROS can evoke the repression of CDH1 to enhance the epithelial-mesenchymal transition (EMT) process through methyl modification of chromatin [ 85 ].…”

Section: Roles Of Ros Molecules In Pcamentioning

confidence: 99%

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

Han

Wang

et al. 2020

BioMed Research International

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Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.

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“…20 In addition, it is well understood that HDAC, DNMT3A, and DNMT3B are major epigenetic factors regulating methylation patterns of GSTP1 and RASSF1 genes which alter the expression of the genes in prostate cancer. 7,21,22 Christopher J. Luskeb in 2002 discussed the association of GSTP1 glutathione S-transferase genotypes with the response to androgen deprivation therapy in patients with advanced prostate cancer. 23 Our results showed a significant increase in GSTP1 and RASSF1 expression in post-treatment specimens (P <0.05).…”

Section: Dovepressmentioning

confidence: 99%

<p>The Effect of Hormone Therapy on the Expression of Prostate Cancer and Multi-Epigenetic Marker Genes in a Population of Iranian Patients</p>

Mohammadi¹,

Irani²,

Salahshourifar³

et al. 2020

CMAR

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Background and Aim: Many recent studies have shown a direct relationship between the decrease in the expression of GSTP1 and RASSF1 with the incidence and progression of prostate cancer. Moreover, the expression level of these genes is greatly affected by epigenetic factors and their methylation pattern. Given the prevalence of prostate cancer and the importance of choosing the best method to inhibit the progression of the disease and provide specific treatment, it is important to evaluate the effect of hormone therapy on the expression of effective prostate cancer genes and epigenetic markers. Patients and Methods: In this case-control study, 35 prostate cancer samples were examined before and after hormone therapy. Following the blood sampling, RNA extraction, and cDNA synthesis, the expression of GSTP1, RASSF1, HDAC, DNMT3A, and DNMT3B was assessed by real-time PCR. Results: The results analysis showed that the expression of GSTP1, RASSF1, and DNMT3B was significantly increased, DNMT3A was significantly decreased (P value<0.05) and HDAC expression did not change significantly (P value=0.19) after hormone therapy. Discussion: Significant changes in the expression of GSTP1, RASSF1, DNMT3B and DNMT3A in the studied samples indicate that these genes are susceptible targets for cancer hormone therapy in Iranian men like in the other populations. Evaluation of gene activity in a larger population of patients may support these findings.

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Epigenetics and prostate cancer: defining the timing of DNA methyltransferase deregulation during prostate cancer progression

Cited by 29 publications

References 56 publications

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Autoimmunity as an Etiological Factor of Cancer: The Transformative Potential of Chronic Type 2 Inflammation

Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

<p>The Effect of Hormone Therapy on the Expression of Prostate Cancer and Multi-Epigenetic Marker Genes in a Population of Iranian Patients</p>

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