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ON CANCER, |
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Cancer, oncogenes and methylation Event description: DNA methylation represents an epigenetic means of inheritance without associated DNA
sequence alterations. Though the function of DNA methylation is still not completely understood, roles have been proposed
for control of gene _expression, chromosomal integrity, and recombinational events. DNA methylation is particularly important
in CpG islands within promoter regions as methylation is associated with transcriptional repression of the associated gene.
Though DNA methylation patterns change during embryogenesis and development, they are thought to be relatively stable in the
adult. Aberrant CpG island methylation has been associated with changes observed in aging and
neoplastic cells. A growing list of genes, including known tumor-suppressor genes, have been shown to have aberrant CpG island
methylation in cancer. This webcast addressed the growing evidence for a pivotal role of DNA methylation in oncogenesis as
well as the methods being employed in this field of research. Dr Charles Cantor
will summarize the state of the work being done and a panel of thought leaders will discuss their work and ideas around where
this field is headed. |
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Cindy D. Davis*,1 and
Eric O. Uthus * National Institutes of Health, National Cancer Institute, Nutritional Sciences Research Group, Rockville,
Maryland 20892–7328; and To whom requests for reprints should be addressed at 1
Nutritional Sciences Research Group, Division of Cancer Prevention, National Cancer Institute, DNA
methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential
role in maintaining cellular function, and changes in methylation patterns may contribute to the development
of cancer. Aberrant methylation of DNA (global hypomethylation
accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can
result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor
genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated
with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved
in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation
because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation
processes. These nutrients include folate, vitamin B12, vitamin B6, methionine, and choline.
However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine)
deficiency in combination causes decreased tissue S-adeno-sylmethionine, global DNA hypomethylation,
hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen
treatment. Other dietary components such as vitamin B12, alcohol, and selenium may modify the response
to inadequate dietary folate. Key Words: DNA methylation • cancer • folate •
selenium • epigenetics Endocrine-Related
Cancer 13 (2) 357-3 Copyright
© 2006 by the Society for Endocrinology. The emerging
roles of DNA methylation in the clinical management of prostate cancer Antoinette S Perry,
Ruth Foley, Karen Woodson1 and Mark Lawler Institute of Molecular Medicine, (Requests for offprints should be addressed to A S Perry; Email:
perryan@tcd.ie
) Aberrant
DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than
20 years. The role
of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution
to the early stages of tumour development to the advanced stages of androgen independence. The most
significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain
family 1A (RASSF1A) and retinoic acid receptor ß2 (RARß2) that become inactivated
through promoter hypermethylation during the course of disease initiation and progression. This has
provided the basis for translational research into methylation biomarkers for early detection and prognosis of
prostate cancer. Investigations into the causes of these methylation events have yielded little definitive
data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein
we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic
modification can be harnessed to address some of the key issues impeding the successful clinical management
of prostate cancer. Chengzhen Ren1, Likun
Li1, Guang Yang1, Terry L. Timme1,2, Alexei Goltsov1, Chenghui Ren1,
Xiaorong Ji1, Josephine Addai1, Hongbin Luo3, Michael M. Ittmann2,3 and Timothy
C. Thompson1,2,4,5 1 Scott Department
of Urology, Baylor College of Medicine, Houston, Texas; 2 Houston Veterans Affairs Medical Center, Houston, Texas;
and Departments of 3 Pathology, 4 Molecular and Cellular Biology, and 5 Radiology, Baylor
College of Medicine, Houston, Texas Cancer Research 64, 969-976, We previously identified and characterized a novel p53-regulated
gene in mouse prostate cancer cells that was homologous to a human gene that had been identified in brain
cancers and termed RTVP-1 or GLIPR. In this report, we document that the human RTVP-1
gene is also regulated by p53 and induces apoptosis in human prostate cancer cell lines. We show that the expression
of the human RTVP-1 gene is down-regulated in human prostate cancer specimens compared with normal
human prostate tissue at the mRNA and protein levels. We further document epigenetic changes consistent
with RTVP-1 being a tumor suppressor in human prostate cancer. DNA Methylation, Chondrogenesis, and Cartilage Degeneration Authors: Aigner, Thomas1; Margarethe Gebhard, Pia1; Sesselmann, Stephan1; Soder, Stephan1; Roach, Helmtrud I.1 Source: Current Rheumatology Reviews, Volume 2, Number 3, August 2006, pp. 221-232(12) Publisher: Bentham Science Publishers Abstract: In the last few years there has been an explosion of research
into epigenetics and, in particular, the roles of DNA methylation in the normal functioning of the mammalian organism as well
as whether changes in methylation status contribute to or cause aberrant gene expression in diseases. While abnormal patterns
of DNA methylation in cancer cells have been intensively investigated, little attention has so far been paid to the role of
DNA methylation in cartilage and cartilage degeneration. This review summarizes the current knowledge of the mechanism of
methylation, its association with transcriptional silencing, possible mechanisms of hyper- and hypomethylation as well as
age- and disease related changes in methylation pattern. We discuss the possible involvement of DNA methylation in chondrogenesis
as well as its potential importance for cartilage degradation. Overall, epigenetic gene regulation has largely been neglected
in cartilage research, but is likely to be an important issue in future. There is increasing evidence that besides cytokines,
growth factors and changes in matrix composition, variations in the genetic methylation pattern might also be important determinators
of the complex gene expression pattern pathognomically observed in osteoarthritic cartilage tissue. The full text article is available for purchase $56.03 plus tax |
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