胰腺癌是高度恶性的消化系统肿瘤，因缺少有效的诊治手段，其五年存活率仅5%。攻克胰腺癌已成为肿瘤研究领域的热点。本实验室自主发现的锌指蛋白ZBTB20在多种组织细胞的增殖、分化和凋亡方面具有重要的调节功能。本项目已证明ZBTB20在胰腺癌组织的导管上皮细胞和多个胰腺癌细胞系的胞核中表达显著降低，并有截短型ZBTB20异位表达于胞浆；野生型ZBTB20过表达则可定位于胞核，并能抑制胰腺癌细胞的增殖，提示ZBTB20功能缺失与胰腺癌的发生发展有关。本项目拟通过临床标本的组织学检测，评估ZBTB20作为胰腺癌分子病理学诊断标志物的价值；利用胰腺导管上皮细胞特异性ZBTB20基因敲除小鼠和裸鼠移植瘤模型，结合胰腺癌细胞学实验，明确ZBTB20是否参与调控胰腺癌的发生发展，并阐明其信号通路；利用表达谱基因芯片和染色质免疫沉淀等技术鉴定其作用的靶基因和位点，以在胰腺癌的发生机制上形成原创性成果。

As one of the highly malignant digestive system neoplasmas, pancreatic ductal adenocarcinoma (PDAC) has poor prognosis because of limited treatment methods. Only approximately 5% of patients survived 5 years after diagnosis. So, new insights into the pathogenesis of this lethal disease and finding of new therapeutic targets have becoming the attractive research field. We have previously found that new zinc finger protein ZBTB20 is pivotal in cell grow,differentiation,apoptosis and tumor modulation. This project has also proved that ZBTB20 expression decreased in the nucleus of the ductal cells of PDAC tissue and several pancreatic cancer cell lines, with truncated ZBTB20 translocating to the cytoplasm. Over-expression of ZBTB20 wild type protein inhibited significantly cell proliferation, with the protein locating in the nucleus. These results indicate the association of ZBTB20 dysfunction with the tumorigenensis of PDAC. Based on the PDAC tissue samples, this proposal will evaluate the possibility of using ZBTB20 in the molecular pathological diagnosis of PDAC. This proposal will also take advantage of the availability of pancreatic ductal cell specific ZBTB20 gene knock-out mice and transplanted tumor model, combined with PDAC cell lines, to figure out whether ZBTB20 functions as the modulator of PDAC tumorigenesis, and finally clarify the underlying molecular events. We will further identify the target genes in PDAC regulated by ZBTB20 using gene expression chips and ChIP-sequence. This study will help to shed light on the unique features of pancreatic biology, providing potential diagnostic and treatment strategies for PDAC.