Generation and characterization of islet cell tumor in pTet-on/pTRE-SV40Tag double-transgenic mice model.
A line of double-transgenic mice that develop neoplasms arising primarily in the pancreas was established. In these mice, the oncogene SV40 T antigen (Tag) was detected in the pancreas with and without the control of Tet-on system. The transgenic mice that developed pancreatic tumors as early as 20 weeks of age showed hypoglycemia on a blood glucose test. Pathological and immunohistochemical characterizations demonstrated that the tumors belonged to neuroendocrine neoplasms arising from pancreatic islets. A change in IGFs/IGF-1R signaling pathway was detected using real-time PCR analysis. A potential association between the IGFs/IGF-1R system and SV40Tag was studied to further explain the cancerogenesis of the double-transgenic mice by Western blot analysis and immunoprecipitation experiments. The results suggest that a Tag transgenic mice model could be used to study the molecular mechanism of the tumorigenesis of islets.
Shen
Qian
Q
Key Lab of Brain Functional Genomics, MOE & STCSM, Shanghai Institute of Brain Functional Genomics, East China Normal University, Shanghai, PR China.
Sun
Qiang
Q
Wei
Xiaoluan
X
Dong
Juan
J
Zhang
Rong
R
Wu
Pu
P
Jin
Yujuan
Y
Feng
Jie
J
Li
Houda
H
Hu
Yinghe
Y
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000032:analysis / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D004195:Disease Models, Animal; D055504:Insulin Receptor Substrate Proteins; D007340:Insulinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D018358:Neuroendocrine Tumors / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism; D013752:Tetracycline / Q000494:pharmacology
D000952:Antigens, Polyomavirus Transforming; D001786:Blood Glucose; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D013002:Somatomedins; D013752:Tetracycline