Hypermethylation of the Prospero-related gene (PROX1) in intra- and extrahepatic cholangiocarcinomas

Aims: The transcription factor Prospero-related gene 1 (PROX1) is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Directed hepatocyte migration into the septum transversum during liver development requires PROX1. Intriguingly, inactivation of PROX1 caused abnormal cellular proliferation via down-regulated expression of the cell-cycle inhibitors CDKN1B and CDKN1C, i.e., p27kip1 and p57kip2, respectively. Aims: We wished to examine whether epigenetic silencing of the PROX1 gene represents a mechanism for the inactivation of this putative tumor suppressor gene in ma…