Department of Urology, Heinrich Heine University, Düsseldorf, Germany
Asian J Androl. 2012 May;14(3):436-50. doi: 10.1038/aja.2011.160. Epub 2012 Feb 27.
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.
表观遗传失调包括 DNA 高甲基化和低甲基化、EZH2（增强子的 zeste 同源物 2）过表达和组蛋白修饰模式的改变，与前列腺癌的进展有关。DNA 甲基化、EZH2 和组蛋白修饰还确保了至少 62 个印迹基因的亲本特异性单等位基因表达。因此，尽管人们很容易推测表观遗传失调可能会扩展到印迹基因，但在癌前列腺中，只有胰岛素样生长因子 2 (IGF2) 的表达变化得到了很好的记录。对前列腺癌中印迹基因的文献和数据库调查表明，尽管表观遗传机制存在全局紊乱，但大多数印迹基因的表达仍然保持不变。相反，选择性的遗传和表观遗传变化似乎导致印迹基因子网络的失活，该子网络可能在前列腺中发挥作用，以限制通过 PI3K/Akt 途径诱导的细胞生长、调节雄激素反应和调节分化。虽然 IGF2 的失调可能构成前列腺癌发生的早期变化，但该印迹基因网络的失活与癌症进展相关。
