Site-Specific Introduction of O-6-Methylguanine into the 12th Codon of the Human Ha-Ras Oncogene and Examination of Its Mutagenic Properties

Journal URL: http://www.sciencedirect.com/science/journal/0165116

DNA methylation-independent regulation of p16 in epithelial cells during mouse mammary gland development

p16 (INK4a) is a known negative regulator of the cell cycle acting up-stream of Rb to inhibit cellular growth. While the contribution of p16 to the tumorigenic process has been extensively studied, little is known about its role in the cellular differentiation process of normal cells. p16 expression in mammary gland epithelial cells and its possible mediation by DNA methylation was explored. The mammary glands from female mice (mus musculus) at distinct developmental stages (virgin, day 10 of lactation and day 3 of involution) were used. The expression pattern of p16 and the DNA methylases, DNMT1, 3a and 3b was investigated by semi-quantitative RT-PCR, in situ hybridization (ISH) and immunohistochemistry. The p16 methylation status was assesed by methylation-specific PCR (MSP). p16 was differentially expressed during distinct developmental stages and its transcriptional regulation was DNA methylation-independent, which was also corroborated by the expression pattern of the three known DNA methyltransferases (DNA MTase). The p16 expression level was elevated during involution compared to the corresponding expression level during lactation. p16 is differentially expressed during normal mammary gland development, which is not mediated by DNA methylation. © 2008 Landes Bioscience

DNA Repair Mechanisms in Colorectal Carcinogenesis

Colon cancer is among the most common cancers and the third cause of cancer deaths worldwide. If detected at an early stage, treatment might often lead to cure. The present review adduces the so far studied alterations in the expression of genes, as well as polymorphisms of genes engaged in DNA repair systems, with particular emphasis on indirect ones that are correlated with colorectal cancer. Such aberrations could be linked to an increased risk for the development of colorectal cancer and might serve as potential targets in the areas of prevention and therapy

Cell death induced by N-methyl-N-nitrosourea, a model SN1 methylating agent, in two lung cancer cell lines of human origin

New therapeutic approaches are needed for lung cancer, the leading cause of cancer death. Methylating agents constitute a widely used class of anticancer drugs, the effect of which on human non small cell lung cancer (NSCLC) has not been adequately studied. N-methyl-N-nitrosourea (MNU), a model SN1 methylating agent, induced cell death through a distinct mechanism in two human NSCLC cell lines studied, A549(p53wt) and H157(p53null). In A549(p53wt), MNU induced G2/M arrest, accompanied by cdc25A degradation, hnRNP B1 induction, hnRNP C1/C2 downregulation. Non-apoptotic cell death was confirmed by the lack of increase in the sub-G1 DNA content, Poly (ADP-ribose) polymerase cleavage and caspase-3, -7 activation. In H157(p53 null), MNU induced apoptotic cell death, confirmed by cytofluorometry of DNA content and immunodetection of apoptotic markers, accompanied by overexpression of hnRNP B1 and C1/C2. Thus, the mechanism of the cell death induced by SN1 methylating agents is cell type-dependent and must be assessed prior treatment. © 2009 Springer Science+Business Media, LLC

Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations

Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of various cancer entities. However, little is known about the role of epigenetic modifications in TENs. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms thymoma, thymic carcinoma, thymic epithelial neoplasm, epigenetics, DNA methylation, HDAC and miRNA were employed and we were able to identify forty studies focused on TENs and published between 1997 and 2021. Aberrant epigenetic alterations seem to be involved in the tumorigenesis of thymomas and thymic carcinomas, with numerous studies reporting on non-coding RNA clusters and altered gene methylation as possible biomarkers in different types of TENs. Interestingly, Histone Deacetylase Inhibitors have shown potent antitumor effects in clinical trials, thus possibly representing effective epigenetic therapeutic agents in TENs. Additional studies in larger patient cohorts are, nevertheless, needed to verify the clinical utility and safety of novel epigenetic agents in the treatment of patients with TENs

Thymic Epithelial Neoplasms: Focusing on the Epigenetic Alterations

Thymic Epithelial Neoplasms (TENs) represent the most common tumors of the thymus gland. Epigenetic alterations are generally involved in initiation and progression of various cancer entities. However, little is known about the role of epigenetic modifications in TENs. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The search terms thymoma, thymic carcinoma, thymic epithelial neoplasm, epigenetics, DNA methylation, HDAC and miRNA were employed and we were able to identify forty studies focused on TENs and published between 1997 and 2021. Aberrant epigenetic alterations seem to be involved in the tumorigenesis of thymomas and thymic carcinomas, with numerous studies reporting on non-coding RNA clusters and altered gene methylation as possible biomarkers in different types of TENs. Interestingly, Histone Deacetylase Inhibitors have shown potent antitumor effects in clinical trials, thus possibly representing effective epigenetic therapeutic agents in TENs. Additional studies in larger patient cohorts are, nevertheless, needed to verify the clinical utility and safety of novel epigenetic agents in the treatment of patients with TENs. © 2022 by the authors. Licensee MDPI, Basel, Switzerland