Pancreatic cancer induced by in vivo electroporation-enhanced sleeping beauty transposon gene delivery system in mouse.
OBJECTIVE
The aim of this study was to establish a pancreatic tumor model of mouse using the electroporation-enhanced Sleeping Beauty (SB) transposon system.


METHODS
The SB transposon system was used in conjunction with electroporation to deliver oncogenes, c-Myc and HRAS, and shRNA against p53 into the mouse pancreas to induce tumors. Oncogenes (c-Myc and HRAS) and shRNA against p53 gene were directly injected into the pancreas of the mouse along with in vivo electroporation applied on the injection site. The tumors were identified grossly and confirmed using animal positron emission tomographic imaging. The tumors were then characterized using histological and immunohistochemical techniques. The expression of the targeted genes (c-Myc, HRAS, and p53) was analyzed by a real-time quantitative polymerase chain reaction.


RESULTS
Pancreatic tumors were successfully induced. The tumor phenotype was a sarcomatoid carcinoma, which was verified through immunohistochemistry. Some cysts or duct-like structures suggested to be metaplastic acinar cells were visible in the induced tumor.


CONCLUSIONS
The SB transposon enhanced with electroporation can readily generate pancreatic tumors in the mice, and thus, this model serves as a valuable resource for the mouse models of pancreatic cancer.
From the *Asan Institute for Life Sciences and College of Veterinary Medicine, Jeju National University, Jeju; †College of Pharmacy, Ewha Womans University, Seoul; ‡Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon; §Asan Institute for Life Sciences and Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center; ∥Department of Biotechnology, Seoul Women's University; ¶University of Ulsan College of Medicine; and #Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
June-Shine
JS
Park
Kyung-Min
KM
Lim
Sung Goo
SG
Park
Sun Young
SY
Jung
Hyun-Ji
HJ
Choi
Do Hee
DH
Lee
Woo-Jin
WJ
Kim
Seung-Mo
SM
Hong
Eun-Sil
ES
Yu
Woo-Chan
WC
Son
D000818:Animals; D004251:DNA Transposable Elements; D018274:Electroporation; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D016259:Genes, myc; D016158:Genes, p53; D011905:Genes, ras; D020022:Genetic Predisposition to Disease; D007150:Immunohistochemistry; D051379:Mice; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D049268:Positron-Emission Tomography; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019895:Transposases / Q000235:genetics*
D004251:DNA Transposable Elements; D034741:RNA, Small Interfering; D019895:Transposases; C494471:sleeping beauty transposase, human