title: Specific changes in the expression of imprinted genes in prostate cancer--implications for cancer progression and epigenetic regulation.
abstract: Epigenetic dysregulation comprising DNA hypermethylation and hypomethylation, enhancer of zeste homologue 2 (EZH2) overexpression and altered patterns of histone modifications is associated with the progression of prostate cancer. DNA methylation, EZH2 and histone modifications also ensure the parental-specific monoallelic expression of at least 62 imprinted genes. Although it is therefore tempting to speculate that epigenetic dysregulation may extend to imprinted genes, expression changes in cancerous prostates are only well documented for insulin-like growth factor 2 (IGF2). A literature and database survey on imprinted genes in prostate cancer suggests that the expression of most imprinted genes remains unchanged despite global disturbances in epigenetic mechanisms. Instead, selective genetic and epigenetic changes appear to lead to the inactivation of a sub-network of imprinted genes, which might function in the prostate to limit cell growth induced via the PI3K/Akt pathway, modulate androgen responses and regulate differentiation. Whereas dysregulation of IGF2 may constitute an early change in prostate carcinogenesis, inactivation of this imprinted gene network is rather associated with cancer progression.
authors.affiliation: Department of Urology, Heinrich Heine University, Düsseldorf, Germany
authors.forename: Teodora
authors.initials: T
authors.lastname: Ribarska
authors.forename: Klaus-Marius
authors.initials: KM
authors.lastname: Bastian
authors.forename: Annemarie
authors.initials: A
authors.lastname: Koch
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Schulz
mesh_terms: D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D063151:Polycomb Repressive Complex 2; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C035170:IGF2 protein, human; D014157:Transcription Factors; D007335:Insulin-Like Growth Factor II; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt