Acceleration of tumor development in the cerebellum of Ptc1+/-mice expressing IGF-I transgene under control of the nestin promoter. (A) Representative immunohistochemical analysis of nestin in preneoplastic lesions detected in Ptc1+/-cerebellum at 3 weeks of age. (B) Frequency of preneoplastic medulloblastoma lesions in cerebellum of Ptc1+/-and Ptc1+/-/IGF-I Tg mice of 3, 5 and 8 weeks of age. (C) The IGF-I transgene caused a significant enhancement in medulloblastoma development (71% in Ptc1+/-/IGF-I Tg mice vs. 43% in Ptc1+/-mice; P < 0.05). (D and E) Representative immunostaining for phosphotyrosine 1316 (pY 1316) IGF-IR in medulloblastomas from Ptc1+/-mice and Ptc1+/-/IGF-I Tg mice. Insets in (D) and (E), higher magnification (100×). (F) Analysis of nestin expression in medulloblastomas from Ptc1+/-mice. (G) Representative immunostaining for IRS1 in medulloblastomas from Ptc1+/-mice. (H) Higher magnification (100×). (I) Immunoblotting of IRS1 in medulloblastomas from Ptc1+/-and Ptc1+/-/IGF-I Tg mice, with relative HSP-70 to control protein loading, and graphic representation of densitometric analysis (lower panel). (L and M) Representative immunostaining for Akt and p-Erk1/2 in medulloblastomas from Ptc1+/-mice. Evaluation of Akt/Pkb (N) and Erk1/2 (O) phosphorylation status by immunoblotting in medulloblastomas from Ptc1+/-and Ptc1+/-/IGF-I Tg mice, and relative graphic representation of densitometric analysis.