Suppression of pancreatic tumor progression by systemic delivery of a pancreatic-cancer-specific promoter driven Bik mutant.
Pancreatic cancer is highly aggressive with extremely poor prognosis. Developing a pancreatic cancer specific promoter (PCSP) is one approach for pancreatic cancer gene therapy. We have modified the promoter of cholecystokinin type A receptor (CCKAR), named CCK/Mpd, which possesses a relatively high activity in pancreatic cancer cells as compared with normal cells. The CCK/Mpd promoter-driven luciferase exhibits a better tumor specific tissue distribution than the CMV promoter-driven luciferase when systemically administered in vivo. Notably, we demonstrate a treatment efficacy by using CCK/Mpd-Bik-DD/liposome in a nude mice xenograft model, suggesting the feasibility of PCSP-based gene therapy in pancreatic cancer treatment.
Li
Zheng
Z
Department of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. zhengli98@yahoo.com
Ding
Qingqing
Q
Li
Yan
Y
Miller
Stephanie A
SA
Abbruzzese
James L
JL
Hung
Mien-Chie
MC
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008081:Liposomes; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011401:Promoter Regions, Genetic; D043886:Receptor, Cholecystokinin A / Q000008:administration & dosage / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; D008081:Liposomes; D043886:Receptor, Cholecystokinin A; D008156:Luciferases