Abstract 1858: Targeting FoxM1 in p53-null tumors

Abstract

Abstract Forkhead box transcription factor FoxM1 is overexpressed in many types of human cancers and promotes tumor development in multiple ways. It is also considered as a potential target for cancer therapy. Because greater than half of the human cancers harbor p53 mutations, we investigate the effect of FoxM1-targeting in spontaneous p53-null tumors. We show that reducing FoxM1 inhibits growth of the p53 null thymic lymphoma and sarcoma cells. In addition, ablation of FoxM1 retards the growth of the p53-null tumors in mouse xenograft model. Moreover, induction of apoptotic cell death is observed in p53 null cells after deletion of FoxM1, accompanied by decreased expression of the FoxM1 target gene Survivin. The ARF26-44 peptide, which inhibits the activity of FoxM1 by targeting it to the nucleolus, is able to effectively induce apoptosis in the p53 null spontaneous tumors. Together, our observations suggest that FoxM1 functions are critical for p53-null tumors and FoxM1 is a therapeutic target of human tumors carrying loss of function p53 mutations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1858. doi:1538-7445.AM2012-1858