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[P2.37]: Formation of striatal circuitry and behaviors in the developing postnatal mouse
Author(s) -
Martins G.J.,
Santos S.S.,
Almeida J.,
Costa R.M.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.167
Subject(s) - citation , humanities , neuroscience , psychology , library science , art , computer science
pathway that regulates Nmyc expression and GNP proliferation in the developing mouse cerebellum (Yun et al, MCB 2007). Furthermore, Mad3 is upregulated in mouse models of medulloblastoma as well as pre-tumor cells, suggesting that Mad3 might also function during tumor biogenesis. Here, we show that Mad3 is upregulated in human medulloblastomas compared with normal cerebellar tissue. Furthermore, altering the levels of Mad3 in human medulloblastoma cell lines results in significant changes in growth rate and tumorigenic potential. Interestingly, S-phase restricted expression of Mad3 is lost during tumor progression, suggesting that persistent expression of Mad3 in GNPs contributes to tumor biogenesis. Current models suggest that only a few atypical cells within the cancerous mass – so-called ‘tumor stem cells’ or ‘tumor propagating cell’ – are responsible for the initiation, growth and recurrence of brain tumors. Intriguingly, the phenotypic and molecular changes we observe upon persistent expression of Mad3 suggest that these cells resemble tumor stem-like cells. Together, our studies support a novel role for Mad3 in tumor biogenesis and suggest that persistent expression of Mad3 reprograms tumor cells towards a more stem-like state.