PDX-1: demonstration of oncogenic properties in pancreatic cancer.
BACKGROUND
Pancreatic-duodenal homeobox 1 (PDX-1) is a transcription factor that regulates embryologic pancreas development and insulin expression in the adult islet; however, it is overexpressed in many types of cancer, including pancreatic cancer. The purpose of this study was to investigate the role of PDX-1 in tumorigenesis in human cells.


METHODS
In vitro cell proliferation, invasion, and transformation were performed in human embryonic kidney cell line (HEK 293), pancreatic cancer cell line MIA PaCa2, and human pancreatic ductal epithelial (HPDE) cells transiently or stably expressing PDX-1 or green fluorescent protein (GFP) PDX-1, with or without cotransfection of PDX-1 short hairpin RNA (shRNA). In vivo tumor formation was carried out in severe combined immunodeficiency (SCID) mice with subcutaneous injection of HEK 293 and MIA PaCa2 stably transfected cells. Cell cycle was analyzed by Western blot or immunostaining. Microarray of RNA from pancreatic adenocarcinoma 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, human pancreatic ductal epithelial (HPDE), and MIA PaCa2 cells versus controls (P < .05), human PDX-1 shRNA reversed these effects. Expression of PDX-1 significantly increased colony formation in HEK 293, HPDE, and MIA PaCa2 cells versus controls in vitro (P < .05). PDX-1 promoted HEK 293 and MIA PaCa2 tumor formation in SCID mice as compared with that of control (P < .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.
Liu
Shi-He
SH
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA.
Patel
Sanjeet
S
Gingras
Marie-Claude
MC
Nemunaitis
John
J
Zhou
Guisheng
G
Chen
Changyi
C
Li
Min
M
Fisher
William
W
Gibbs
Richard
R
Brunicardi
F Charles
FC
D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D009857:Oncogenes; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation
D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein