Proliferative Inflammatory Atrophy of the Prostate

Another, more attractive, hypothesis maintains that widespread chronic inflammation, atrophy, and regeneration in the prostate might provide the fertile ground of stress and genome damage that lead to the development of multiple prostate cancer lesions that are heterogeneous in their age and aggressiveness. The identification of highly prevalent PIA lesions lends much support to this hypothesis, and offers direct evidence for a link between prostate inflammation and carcinogenesis. As mentioned...

Cpg Island Hypermethylation Changes During Prostate Cancer Progression And Metastasis

Srinivasan Yegnasubramanian and William G. Nelson The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract Recent studies have implicated the dysregulation or maladaptation of epigenetic mechanisms to be a central feature of prostate carcinogenesis. Hypermethylation of CpG islands (CGI), clusters of CpG dinucleotides frequently found at gene regulatory regions, has been demonstrated to be one of the most frequent somatic genome...

Methylationassociated Silencing In Cancer Progression Involves Abnormal Histone Modifications

It has been widely proposed that the hypermethylated CpG islands will attract methyl-DNA binding activities that will later recruit corepressor complexes that modify the structure of the chromatin to produce a transcriptionally silenced state (18, 38). The presence of different changes in the acetylation, methylation and phosphorylation status of histone, the denominated histone code (39), is fundamental to the determination of the active or silenced status of any given gene. Regarding tumor...

Promoter Hypermethylation Of Cancer Related Genes In Breast Cancer

Cancer is the result from a multistep process characterized by the accumulation of genetic and epigenetic hits leading to uncontrolled growth and ultimately to the acquisition of metastatic potential (Figure 1B). Three types of genes are involved in carcinogenesis oncogenes, tumor suppressor genes (TSGs) and stability (caretaker) genes. These cancer related genes are involved in a series of pathways that control the basic function of the cell proliferation, communication with neighboring cells...

Cpg Island Hypermethylation In Breast Cancer Progression And Metastasis

Research Department, Molecular Oncology Laboratory, IRCCS Casa Sollievo della Sofferenza, San GiovanniRotondo (FG), Italy Abstract Breast cancer is the most common malignancy in women and comprises 18 of all female cancers. The incidence of breast cancer increases with age and in the western countries the disease is the single most common cause of death among women aged 40-50, accounting for about a fifth of all deaths in this age group. The advent of mammography screening has led to an...

Metastatic Prostate Cancer

Very few studies have described CGI hypermethylation patterns in metastatic prostate cancers, due to the difficulty in obtaining metastatic cancer tissue. Surgical resection of metastatic deposits of prostate cancer does not enhance survival from the disease significantly. Therefore, most patients with refractory, metastatic prostate cancer are not candidates for further surgical intervention. Therefore, the few studies that have examined CGI hypermethylation patterns in metastases obtained...

Mca3d

Global DNA methylation in a mouse skin tumor progression model. A. Representative partial electropherograms (cytosine and methylcytosine peaks) of enzymatically hydrolyzed genomic DNA extracted from normal skin (NS) and MDA3D, PDV and CarC cell lines. B. Double-staining of MCa3D, PDV and CarC cells with DAPI, a chromatin marker, and mouse monoclonal antibodies against 5mC show a clear nuclear redistribution of 5mC associated with cell tumorigenicity. Bar 10 am. C. Orthogonal...

Candidate Genes In Tumor Progression And Metastasis

Cancer epigenetics studies cannot be fully understood if we do not appreciate the relevance of the silencing of tumor-suppressor genes associated with CpG island hypermethylation and their histone modifications and chromatin-linked changes. In such a context, the multistage mouse skin progression model is also demonstrably useful for defining the chronological inactivation pattern of tumor-suppressor genes with methylation-associated silencing that are known to be hypermethylated in human...

Evasion from Apoptosis

Programmed cell death (apoptosis) is a mechanism implicated in the control of cell number and in the elimination of dysfunctional cells. Extracellular death signals as well as intracellular stimuli like genotoxic damage can initiate the apoptotic program (190). A major checkpoint in the cell death-signaling cascade is mediated by the BCL-2 family of proteins, which is characterized by members with pro-apoptotic (BAX) or anti-apoptotic (BCL-2) function. Interestingly the Bax gene was recently...

Cpg Island Hypermethylation And Lung Cancer Invasion And Metastasis

Sathyanarayana and Adi F. Gazdar Hamon Center for Therapeutic Oncology Research, Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, USA Abstract Invasion and metastasis are biological hallmarks of malignant tumors, and metastases are the major cause of cancer deaths. Invasion and destruction of BM is the earliest step in the multi-step process of metastases and it is the earliest morphological feature of invasive tumors. Disruption of...

Models For The Development Of Prostate Cancer Metastases

The mechanisms underlying the dissemination of primary prostate cancer and establishment of metastatic deposits is a topic of great interest since these lesions are ultimately responsible for the vast majority of prostate cancer deaths. It is clear from clinical observations that prostate cancers have a predilection to metastasize to a distinct set of anatomical organ systems, such as lymph node, bone and liver. The first formal hypothesis suggesting an explanation for the non-random...

Molecular Mechanisms In The Generation And Propagation Of Aberrant Dna Methylation Patterns In Prostate Cancer

In our discussions thus far, we have been continually alluding to a fundamental paradox concerning CGI hypermethylation in prostate cancer initiation and propagation DNA methylation processes appear to be dysregulated enough to cause hypermethylation of CGIs at multiple genes yet, the same DNA methylation processes have high enough fidelity that they can maintain the acquired changes in CGI hypermethylation through every step of prostate cancer initiation and progression. This observed paradox...

From the Normal Breast to Cancer the Concept of Breast Cancer Stem Cell

It is now well established that breast cancer originates from the TDLU, but it is not clear which are the cells targeted by tumorigenesis (6-10). A recent interesting hypothesis based on experimental evidence from tumor subpopulation transplantation and animal models suggests that mammary tumors may derive from adult breast stem cells (2, 11). The involvement of stem cells in carcinogenesis was suggested more than 30 years ago (10, 1214), but only recently the tools of stem cell biology were...

Cpg Island Hypermethylation Changes During Prostate Cancer Initiation And Progression

Prostate Cancer Disease Progression

In 1994, Lee et al. demonstrated that hypermethylation of CGI sequences within the regulatory region of GSTP1, which encodes the pi-class glutathione S-transferase (GST) enzyme, is an extremely frequent feature of human prostate cancer (49, 50). Since that initial study, numerous groups have independently corroborated these findings using a wide array of techniques applied to numerous prostate cancer DNA sources, including prostatectomy specimens, prostate autopsy specimens, prostate biopsy...

Mouse Skin Multistage Carcinogenesis Model That Unmasks Epigenetic Lesions Responsible For Metastasis

Cancer Epigenetics Laboratory, Molecular Pathology Programme, Spanish National Cancer Centre (CNIO), Madrid, Spain Abstract Although there is a wide range of accepted models of tumorigenesis involving genetic lesions, the timing and hierarchy of epigenetic alterations associated with tumor progression and metastasis are still poorly understood. In this regard, the best characterized mouse carcinogenesis system, the multistage skin cancer progression model, has recently been used to identify...

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Esteller ed. , DNA Methylation, Epigenetics and Metastasis, 1-8. 2005 Springer. Printed in the Netherlands. described the exquisite profile of hypermethylation that occurs in primary human tumors 2 . Furthermore, the number of hypermethylated genes increases with the malignant potential 4 . In recent years, we and other groups have extensively mapped an increasing numbers of gene CpG islands aberrantly hypermethylated in cancer 2,3 . Such DNA methylation mapping has brought to light the...