254 Insulin-like growth factor 2 mRNA binding protein (IGF2BP1) regulates a set of target genes important in basal cell carcinoma development

Dysregulation of the Hedgehog (Hh) signaling pathway is implicated in development many cancers including BCC. PTCH1 and SMO are critical players Hh GLI1 transcriptional activator through which mediated. Mutation or have been shown to constitutively activate pathway. Active canonical Wnt has also be required for pathway–driven We previously identified a novel mechanism by regulates outcome signaling. show that IGF2BP1, direct target could bind Gli1 mRNA upregulate its expression. This regulation IGF2BP1 was independent upstream signal. hypothesized Wnt-dependent induction genes contribute BCC development. propose inhibition will reduce expression activity as well targets therefore prevent To test this, we generated skin specific knockout mouse model Ptch1tm1Mps/J background using Cre/loxp system. inhibited tamoxifen injection (75mg /kg) five consecutive days. Mice were subsequently exposed UVB irradiation (240 mJ/cm2) three times week 44 weeks. analyzed tumors developed control experimental mice observed significantly reduced lesions (P<0.05). The Gli2 same samples However, Ptch1 not affected inhibition. targets, c-myc βTrCP1 went might upregulating only Gli1, but additional promote progression disease.