近年来研究发现活化诱导胞嘧啶核苷脱氨酶（AID）是一种在B细胞中诱导体细胞高度突变和免疫球蛋白类别转换的关键酶，而慢性炎症刺激能够诱导上皮细胞异常表达AID，进而促进上皮细胞癌变。我们前期研究发现膀胱尿路上皮癌细胞能够表达AID和 IgG1，IgG1具有促进癌细胞增殖的效应，我们推测尿路上皮细胞内AID可能通过激活重组活化基因-1（RAG-1）编辑调控IgG1，并诱导相关癌基因表达。本课题拟检测膀胱尿路上皮细胞、癌细胞和膀胱炎组织标本中AID、RAG-1和IgG1的表达相关性，PCR-单链构象多态性和基因测序确定癌变相关基因突变位点和频率；将AID基因通过质粒表达载体转染膀胱尿路上皮永生细胞和通过siRNA沉默癌细胞中AID，了解 AID改变后对IgG1及p53、ras基因的影响；进一步从NF-κB信号途径阐明AID异常激活的机制；将为以AID为靶点的膀胱尿路上皮细胞癌的防治提供依据。

For the past few years, some studies showed activation-induced cytidine deaminase (AID) is only expressed in activated B cells in normal conditions , and it is the most important enzyme involved in induced somatic hypermutation (SHM) by converting dC to dU and produced Class Switching recombination in immunoglobin G1 gene. Recently research studies yet indicate chronic inflammation stimulus can induce aberrant expression of AID in epithelium, AID might trigger and promote human tumorigenesis by an enhanced genetic susceptibility to mutagenesis. Our prophase study detected IgG1 was significantly expressed in bladder uroepithelial cell carcinoma, IgG1 could promote cancer cell proliferation. Those findings led us to hypothesize that AID may induce correlated oncogene expression in editting and regulating immunoglobin G1 gene by activated recombination activating gene-1 (RAG-1) during human bladder uroepithelial cells carcinogenesis. In the proposed project , we will detect the expression of the correlation between mRNA and protein of AID,RAG-1 and IgG1in bladder cancer cell, normal uroepithelial cells and clinical specimen of cystitis (including model of SD rats) . We then will examine correlated oncogene genetic （ p53 and ras）mutation site and frequency by PCR-SSCP and gene sequencing analyses in bladder cancer cell and cystitis glandularis, and investigate the correlation between AID expression and correlated oncogene mutantion; AID cDNA will be inserted into a pEGFP vector to construct an AID expression vector, then AID expression vector will be transfected in SV-HUC-1 cell lines, and AID expression will be silenced by siRNA technology in bladder uroepithelial carcinoma cells，to study the effect of AID expression on p53 and c-myc mutantion in bladder urothelium cells. Finally, we will clarity the signaling mechanism of AID expression via NF-κB. We expect to provide a new evidence for biological behaviour of tumorigenesis and evolutionary in bladder cancer, and to investigate a new approach for bladder cancer therapy and prevention in the future.