Non-muscle invasive bladder cancer (NMIBC) remains a very troublesome cancer to care because of high recurrence rates. In the previous study, we characterized a gene expression dataset from 102 NMIBC patients of the Korean cohort to identify a signature associated with disease recurrence. In recurrent bladder cancers, the expression of FOXM1 (Forkhead Box M1) was increased compared to primary cancers. Although there is a relationship between DNA repair pathway and FOXM1, it remains unclear whether FOXM1 is associated with DNA repair mediated cancer recurrence. To investigate this association, we used five different human bladder cancer cell lines to examine the expression level of FOXM1. Two cancer cell lines (5637 and EJ cells) showed the increased level of FOXM1 than other three cancer cell lines (UC5, LD611 and UC9 cells). We examined the chemoresistance with chemotherapy reagent (Doxorubicin) and checked the possible regulation of DNA repair pathway by FOXM1 in these cell lines. The cell lines which elevated FOXM1 expression showed high expression levels of Non-homologous end joining (NHEJ) pathway genes (Ku70, Ku80, LIG4 and XRCC4). To examine the direct interaction between the FOXM1 and NHEJ pathway genes, the binding activity was checked by a promoter assay and chromatin immunoprecipitation. We revealed that the expression levels of NHEJ pathway genes are elevated on activation of exogenous FOXM1. Therefore, we suggest a novel activity of FOXM1 has a role in cancer recurrence through the NHEJ pathway in bladder cancer cells.

Citation Format: Yun-Gil Roh, Se-Ra Lee, Won-Tae Kim, Seon-Kyu Kim, In-Sun Chu, Sun-Hee Leem. FOXM1 regulates doxorubicin resistance through the non homologous end joining pathway and is associated with recurrence of bladder cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3408. doi:10.1158/1538-7445.AM2014-3408