Open AccessInvolvement of insulin‐like growth factor‐insulin receptor signal pathway in the transgenic mouse model of medulloblastoma
Author(s) -
Sun Qiang,
Wei Xiaoluan,
Feng Jie,
Zhang Rong,
Shen Qian,
Dong Juan,
Jin Yujuan,
Dong Suzhen,
Li Houda,
Hu Yinghe
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00679.x
Subject(s) - medulloblastoma , genetically modified mouse , transgene , biology , cancer research , irs1 , growth factor , insulin receptor , insulin like growth factor , doxycycline , receptor , microbiology and biotechnology , insulin , endocrinology , gene , genetics , insulin resistance , antibiotics
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. ( Cancer Sci 2008; 99: 234–240)