A mouse model of MYCN-driven retinoblastoma reveals MYCN-independent tumor reemergence.

ABSTRACT: The most frequent focal alterations in human retinoblastoma are mutations in the tumor-suppressor gene retinoblastoma (RB) and amplification of the oncogene MYCN. Whether MYCN overexpression drives retinoblastoma has not been assessed in model systems. Here, we have shown that Rb inactivation collaborates strongly with MYCN overexpression and leads to retinoblastoma in mice. Overexpression of human MYCN in the context of Rb inactivation increased the expression of MYC-, E2F-, and ribosome-related gene sets, promoted excessive proliferation, and led to retinoblastoma with anaplastic changes. We then modeled responses to MYCN-directed therapy by suppressing MYCN expression in MYCN-driven retinoblastomas. Initially, MYCN suppression led to proliferation arrest and partial tumor regression wit

SUBMITTER: Wu N 

PROVIDER: S-EPMC5330763 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature