转录因子E2F-1在不同类型肿瘤中有不同的作用，在弥漫大B细胞淋巴瘤（DLBCL）中E2F-1的表达与较好预后相关，但具体机制尚不清楚。课题组前期工作证实，E2F-1在不同DLBCL亚型中表达存在明显差异，其表达与维生素受体（VDR）的表达呈正相关，在VDR启动子区域存在E2F-1结合位点，上调E2F-1可引起VDR表达上调，故提出E2F-1可能是DLBCL的一种生长抑制因子，并调控VDR转录表达这一假设。课题组以基因转染、移植瘤、条件性基因敲除作为主要技术手段，通过体内、外实验，寻找E2F-1/VDR信号通路抑制DLBCL生长的直接证据，探索E2F-1对VDR的转录调控机制，阐明E2F-1在不同DLBCL亚型中的作用，揭示E2F-1/VDR信号通路在DLBCL发生发展中的作用，课题的实施有望为DLBCL尤其是ABC亚型患者的治疗提供一种新的思路和药物作用新靶点。

E2F transcription factor 1 (E2F-1) acts as different roles in different types of tumors. Although the expression of E2F-1 correlated with favor prognosis in diffuse lager B-cell lymphoma (DLBCL), its concret mechanism remains unclear. Our preparatory work has demonstrated the disparation of E2F-1 expression among DLBCL subtypes, and there existed some positive relationship between the expression of E2F-1 and Vitamin D Receptor(VDR). In the region of VDR promoter, there were two E2F-1 binding sites, E2F-1 could bind directly to the VDR promoter, and the up-regulation of E2F-1 will result in up-regulation of VDR. In this study, we suppose that E2F-1 may be a tumor suppressor which regulated the transcriptional expression of VDR in DLBCL. We will use multiple techniques mainly including gene transfection, xenografted tumor and conditional gene knockout to construct conditional gene knockout mouse model, so as to seek the direct evidence of suppression of E2F-1/VDR signaling pathway in DLBCL, and to investigate the mechanisms of transcriptional regulation of E2F-1 to VDR, and to reveal the carcinogenesis and development of E2F-1/VDR signaling in DLBCL. It could lead to the identification of potential therapeutic targets for designing novel effective therapies for DLBCL, especially for ABC subtype.