Involvement of insulin-like growth factor-insulin receptor signal pathway in the transgenic mouse model of medulloblastoma.
A transgenic mouse model expressing Simian virus 40 T-antigen (SV40Tag) under the control of a tetracycline system was generated. In this model, a cerebellar tumor was developed after doxycycline hydrochloride treatment. Real time-polymerase chain reaction and immunohistochemistry results indicated that the SV40Tag gene was expressed in the tumor. Pathological analysis showed that the tumor belonged to medulloblastoma. Further molecular characterization of the tumor demonstrated that the insulin-like growth factor (IGF) signaling pathway was activated. We also found that the SV40Tag could bind and translocate insulin receptor substrate 1 into the nucleus in primary cultured tumor cells. The interaction between the IGF pathway and SV40Tag may contribute to the process of malignant transformation in medulloblastoma. This transgenic animal model provides an important tool for studies on the signal pathways involved in the preneoplastic process in medulloblastoma and could help to identify therapeutic targets for brain tumors.
Sun
Qiang
Q
Key Laboratory of Brain Functional Genomics, Shanghai Institute of Brain Functional Genomics, East China Normal University, 200062, Shanghai, China.
Wei
Xiaoluan
X
Feng
Jie
J
Zhang
Rong
R
Shen
Qian
Q
Dong
Juan
J
Jin
Yujuan
Y
Dong
Suzhen
S
Li
Houda
H
Hu
Yinghe
Y
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002528:Cerebellar Neoplasms / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004318:Doxycycline / Q000633:toxicity; D005260:Female; D055504:Insulin Receptor Substrate Proteins; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011972:Receptor, Insulin / Q000378:metabolism*; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013539:Simian virus 40 / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D017451:Receptors, Somatomedin; D011972:Receptor, Insulin; D004318:Doxycycline