Identification of Epigenetic Changes in Prostate Cancer using Induced Pluripotent Stem Cells.

摘要

Infection of human prostatic epithelial cells with lentiviruses expressing Oct4, Sox2, Klf4 and c-myc generated induced pluripotent stem cells (iPSCs). Comparison of gene and protein expression of these prostatic iPSCs and embryonic stem cells (ESCs) revealed similarities but also some differences. Prostate iPSCs could be induced into endodermal, ectodermal, and mesodermal lineages, confirming pluripotency. In response to inductive factors, prostate iPSCs differentiated into basal and secretory prostatic epithelial cells in vitro and in vivo. Methylation profiling revealed epigenetic changes that occur temporally as pluripotent cells convert first to basal cells, then transit amplifying cells expressing androgen receptor (AR) I and finally secretory cells expressing prostatespecific antigen (PSA). Prostatic iPSCs provide a novel model for delineating the epigenetic changes involved in regulation of lineage differentiation of the prostatic epithelium.