Abstract
Abstract Introduction. FOXP1 forkhead transcription factor is one of the markers of activated B-cell-like (ABC) subgroup of diffuse large B-cell lymphoma (DLBCL). High level expression of FOXP1 has been reported to have a poor prognosis and nine different truncated isoforms of N-terminally truncated FOXP1 were found apart from full length FOXP1. However, the biologic roles of isoforms are not fully investigated. In this study, oncogenic effect of FOXP1 smaller isoform3 (FOXP1.3) was evaluated and complementary regulation between FOXP1 and FOXP1.3 was investigated. Methods. Various B-cell lymphoma cell lines (BJAB, OCI-Ly-19, SU-DHL-6, U2932, U2940 and Daudi) were used to evaluate FOXP1 isoforms by immunoblotting and RT-PCR. Two different cell lines, U2932 (ABC-DLBCL) and U2940 (primary mediastinal B-cell lymphoma) cells were exposed to FOXP1-specific siRNA and transfected with FOXP1.3 plasmid tagged with flag for up to 48 hr, respectively. After silencing and over-expression of FOXP1, cell proliferation was measured by colorimetric technique. Therapeutic effects were also confirmed by the treatment of monoclonal anti-CD20 antibody, rituximab at a dose of 10 μg/106 cells for 3 days. Results. Differential patterns of expression of FOXP1 isoforms were detected in various DLBCL cell lines on both protein and mRNA levels. U2940 cells exhibited high level of endogenous FOXP1.3 compared with other cell lines. The suppression of FOXP1 by siRNA led to the over-expression of FOXP1.3 in DLBCL cell lines. Up-regulation of FOXP1.3 showed approx. 2.5 folds increase of cell proliferation by colorimetric assay. This was due to induction of survival pathways involving NF-κB and NFAT2 transcriptional factors, which are nuclear transcriptional factors that represent major neoplastic events in DLBCL. Activation of FOXP1.3 was also observed after exposure to rituximab. Rituximab suppressed FOXP1 and dramatically increased expression levels of FOXP1.3 simultaneously in a time-dependent manner. Conclusion. A novel oncogenic property of FOXP1.3 and its complementary regulation with FOXP1 in DLBCL cell lines was observed. These data also suggest a possible mechanism of resistance to rituximab treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-120. doi:10.1158/1538-7445.AM2011-LB-120
Published Version
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