Abstract 2048: Evidence that MTAP acts as a genetic switch to inhibit tumor formation

Abstract

Abstract Methylthioadenosine Phosphorylase (MTAP) deficiency is widely observed in a variety of human tumor and tumor derived cell lines, suggesting that MTAP may play a role in tumorigenesis. It is an enzyme that catalyzes phosphorylation of 5′deoxy-5′-methylthioadenosine (MTA), a byproduct of in vivo polyamine biosynthesis. To elucidate the mechanism by which MTAP inhibits tumor formation, we created a MCF-7 breast cancer derived cell line that expresses MTAP under a doxycycline (DOX) regulated promoter. In this cell line MTAP expression was undetectable in the absence of DOX and could be detected as early as 4 hours after DOX induction. MTAP expression caused a decrease in cell proliferation, soft-agar colony formation, and cell migration. Microarray studies revealed several genes that were regulated by MTAP. For two of the genes that were identified, AGPAT4 and IGFBP1, we examined the relationship between their mRNA levels and MTAP mRNA levels by qRT-PCR. Surprisingly, a brief pulse of MTAP expression was able to alter mRNA levels of these genes and this change in mRNA persisted even when MTAP RNA levels were no longer detectable. Our findings show that MTAP expression suppresses tumorigenesis and it may act as a genetic switch. Citation Format: Baqing Tang, Warren Kruger. Evidence that MTAP acts as a genetic switch to inhibit tumor formation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2048. doi:10.1158/1538-7445.AM2015-2048