Li Leyi, Connelly Michele C, Wetmore Cynthia, Curran Tom, Morgan James I
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Cancer Res. 2003 Jun 1;63(11):2733-6.
Cancer cells escape from growth control by accumulating genetic and epigenetic alterations. In rare instances, epigenetic changes alone are oncogenic. Furthermore, agents that modify DNA methylation or chromatin structure can restore a normal phenotype to cells harboring oncogenic mutations. However, it is unclear to what extent epigenetic reprogramming can reverse oncogenesis. Using somatic nuclear transfer, we show that medulloblastomas arising in Ptc1+/- mice can direct preimplantation development. Additionally, blastocysts derived from medulloblastoma nuclei form postimplantation embryos with typical cell layers. Thus, tumor cells can be epigenetically reprogrammed into normal cell types. This approach could lead to a general strategy for assessing genetic and epigenetic contributions to tumorigenesis.
癌细胞通过积累基因和表观遗传改变来逃避生长控制。在极少数情况下，仅表观遗传变化就具有致癌性。此外，改变DNA甲基化或染色质结构的试剂可以使携带致癌突变的细胞恢复正常表型。然而，尚不清楚表观遗传重编程在多大程度上可以逆转肿瘤发生。利用体细胞核移植，我们发现Ptc1+/-小鼠中产生的髓母细胞瘤可以指导植入前发育。此外，源自髓母细胞瘤细胞核的囊胚形成具有典型细胞层的植入后胚胎。因此，肿瘤细胞可以通过表观遗传重编程转变为正常细胞类型。这种方法可能会带来一种评估遗传和表观遗传对肿瘤发生贡献的通用策略。
