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Epigenetic Mechanisms for Progression of Prostate Cancer

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Abstract

Epigenetic mechanisms may be the main driving force for critical changes in gene expression that are responsible for progression of prostate cancers. The three most extensively characterized mechanisms for epigenetic gene-regulation are (i) changing patterns of DNA methylation, (ii) histone acetylations/deacetylations, and (iii) alterations in regulatory feedback loops for growth factors. Several studies have indicated that DNA hypermethylation is an important mechanism in prostate cancer for inactivation of key regulatory genes such as E-cadherin, pi-class glutathione S-transferase, the tumor suppressors CDKN2 and PTEN, and IGF-II. Similarly, histone acetylations and deacetylations are frequently associated respectively with transcriptional activation (e.g. IGFBP-2 and p21) and repression (e.g. Mad:Max dimers) of genes linked to prostate cancer progression. Recently, histone acetyltransferase and deacetylase activities have been shown to be intrinsic with transcriptional coregulator proteins that bind to steroid receptors (e.g. SRC-1 and PCAF). Changes in regulatory feedback loops for growth factors with prostate cancer progression tend toward shifts from paracrine to autocrine control where the receptor and ligand are produced by the same cell. While there are several examples of this progression pattern in prostate tumors such as with IGF, FGF, TGF-α and their respective receptors, the precise mechanism (i.e. epigenetic or mutational) is less certain. In the context of treatment options, the contribution of mutational versus epigenetic events to prostate cancer progression is an improtant consideration. Irreversible genetic changes are likely to be less amenable to therapeutic control than are epigenetic ones.

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  1. Department of Surgery, University of British Columbia and The Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada

    Paul S. Rennie & Colleen C. Nelson

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Rennie, P.S., Nelson, C.C. Epigenetic Mechanisms for Progression of Prostate Cancer. Cancer Metastasis Rev 17, 401–409 (1998). https://doi.org/10.1023/A:1006121219097

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