PDX-1: Demonstration of Oncogenic Properties in Pancreatic Cancer

Background—Pancreatic-duodenal homeobox 1 (PDX-1) is a transcription factor which regulates embryologic pancreas development and insulin expression in the adult islet, however it is overexpressed in many types of cancer, including pancreatic cancer (PC). The purpose of this study is to investigate the role of PDX-1 in tumorigenesis in human cells. Methods—In vitro cell proliferation, invasion and transformation were performed in HEK 293, MIA PaCa2 and HPDE cells with transient or stable expressing PDX-1 or GFP PDX-1, with or without co-transfection of PDX-1 shRNA. In vivo tumor formation was carried out in SCID mice with sq injection of HEK 293 and MIA PaCa2 stably transfected cells. Cell cycle was analyzed by Western blot or immunostaining. Microarray of RNA from PANC-1 cells with and without PDX-1 shRNA was performed and analyzed. Results—Transient and stable expressing PDX-1 significantly increased cell proliferation and invasion in HEK 293, HPDE and MIA PaCa2 cells vs controls (p<0.05), hPDX-1 shRNA reversed these effects. Expression of PDX-1 significantly increased colony formation in HEK 293, HPDE and MIA PaCa2 cells vs controls in vitro(P<0.05). PDX-1 promoted HEK 293 and MIA PaCa2 tumor formation in SCID mice as compared to that of control(P<0.05). PDX-1 overexpression disrupted cell cycles proteins. PDX-1 expression was confirmed by western blot and tracked by viewing of GFP-PDX-1 expression. Microarray data support an oncogenic role of PDX-1 in pancreas cancer cells. Conclusions—PDX-1 induced increased cell proliferation, invasion, and colony formation in vitro, and resulted in markedly increased HEK 293 and MIA PaCa2 tumor formation in SCID mice. These data suggest that PDX-1 is a potential oncogene that regulates tumorigenesis.