Prostate Cancer Epigenetics: A Review on Gene Regulation

Abstract

Prostate cancer is the most common cancer in men in western countries, and its incidence is increasing steadily worldwide. Molecular changes including both genetic and epigenetic events underlying the development and progression of this disease are still not well understood. Epigenetic events are involved in gene regulation and occur through different mechanisms such as DNA methylation and histone modifi cations. Both DNA methylation and histone modifi cations affect gene regulation and play important roles either independently or by interaction in tumor initiation and progression. This review will discuss the genes associated with epigenetic alterations in prostate cancer progression: their regulation and importance as possible markers for the disease.

Are biomarkers evaluated in biopsy specimens predictive of prostate cancer aggressiveness?

“…PCa is generally an indolent disease, and most cases of prostate cancer are slow-growing and unlikely to spread, due to immediate treatment with surgery or radiation. These therapeutic strategies are associated with short-and 1993; Diaw et al 2007;Ganz et al 2011Ganz et al , 2012Cuzick et al 2014). Indeed, in most cases, men with PCa died and not because of the tumor.…”

Modulation of One-Carbon Metabolism by B Vitamins: Implications for Transformation and Progression of Prostate Cancer

“…As prostate tissue progresses from proliferative inflammatory atrophy (PIA) and PIN through hormone refractory metastatic disease a series of hypermethylated genes appear, see Figure 23 (Li & Dahiya, 2007). As tumors develop androgen independence, methylation of androgen and estrogen receptor genes becomes evident (Diaw et al, 2007;Sasaki et al, 2002). …”

“…Genomic DNA aberrant methylation of tumor specific genes is almost always abnormal in malignant and transforming cells. These changes progress during carcinogenesis through clinical metastases and are more frequent than chromosomal mutations (Bastian et al, 2004;Diaw et al, 2007;Li & Dahiya, 2007;Perry et al, 2006;Sasaki et al, 2002;Song et al, 2002). Epimethylation's relevance to the genesis of prostate cancer is illustrated by sequential hypermethylation and hypomethylation of genes as prostate tumors dedifferentiate and clinically progress over time (Maruyama et al, 2002).…”

“…The cell DNA methylome changed to produce the more aggressive phenotype in vitro; cells became anchorage-independent and showed reduced sensitivity to folate depletion. There is mounting biochemical and epidemiological support that cancers of the prostate may result in part from micronutrient imbalance leading to mutations and the aberrant epimethylome triggering abnormal gene expression (van Engeland et al, 2003;Cooper & Foster, 2009;Diaw et al, 2007;Ernst et al, 2002;Esteller, 2007;Esteller, 2008;Li et al, 2005;Li & Dahiya, 2007;Maruyama et al, 2002;Perry et al, 2006;Sasaki et al, 2002;Shukeir et al, 2006;Yegnasubramanian et al, 2008). Folate metabolizing enzyme polymorphisms complicate the overall picture (Cai et al, 2010) ( Figure 9) through interaction with B vitamin metabolism causing results of epidemiological studies to be inconsistent; this has been extensively reviewed Kim, 2004;Kim, 2005;Sanderson et al, 2007;Smith et al, 2008;Sohn et al, 2009 Lowe et al, 1993;Moran & Colman, 1984;Shane, 2010;Sun et al, 2001;Ward & Nixon, 1990).…”

“…Only through gene expression do observable phenotypic changes become apparent. The prostate is under environmental controls mediated through DNA and histone methylation (Diaw et al, 2007;Esteller, 2008 Each tumor subtype can be assigned a DNA hypermethylome profile, a CpG island hypermethylation pattern that closely defines a specific cancer. It is estimated that each tumor contains between 100-400 tumor-specific hypermethylated CpG islands (Esteller, 2007).…”