Insulin-like growth factor 2 is required for progression to advanced medulloblastoma in patched1 heterozygous mice.
Insulin-like growth factor 2 is required for progression to advanced medulloblastoma in patched1 heterozygous mice.
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DOI：
10.1158/0008-5472.can-08-2135
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发表时间：
2008-11-01
期刊：
影响因子：
11.2
通讯作者：
Scott, Matthew P.
中科院分区：
文献类型：
--
作者：
Corcoran, Ryan B.;Raveh, Tal Bachar;Barakat, Monique T.;Lee, Eunice Y.;Scott, Matthew P.
Medulloblastoma (MB) can arise in the cerebellum due to genetic activation of the Sonic Hedgehog (Shh) signaling pathway. During normal cerebellum development, Shh spurs the proliferation of granule neuron precursors (GNPs), the precursor cells of MB. Mutations in the Shh receptor gene, patched1 (ptc1+/-), lead to increased MB incidence in humans and mice. MB tumorigenesis in mice heterozygous for ptc1+/- shows distinct steps of progression. Most ptc1+/- mice form clusters of pre-neoplastic cells on the surface of the mature cerebellum that actively transcribe Shh target genes. In ∼15% of mice, these pre-neoplastic cells will become fast-growing, lethal tumors. It was previously shown that the loss of function of insulin-like growth factor 2 (igf2) suppresses MB formation in ptc1+/- mice. We found that igf2 is not expressed in preneoplastic lesions but is induced as these lesions progress to more advanced MB tumors. Igf2 is not required for formation of pre-neoplastic lesions, but is necessary for progression to advanced tumors. Exogenous Igf2 protein promoted proliferation of MB precursor cells (GNPs) and a MB cell line, PZp53MED. Blocking igf2 signaling inhibited growth of PZp53MED cells, implicating igf2 as a potential clinical target.
