寻找新的肿瘤抗原基因和表达蛋白，明确其生物学功能和作用机制是发展肿瘤靶向治疗的关键。肿瘤抗原OVA12是应用重组cDNA表达文库血清学分析技术筛选得到的一个新的蛋白分子，分子量为12KD。申请人在以往研究中证实肿瘤抗原OVA12在肿瘤细胞（组织）中特征性高表达，具有促进肿瘤细胞增殖的重要生物学功能。应用基因芯片等高通量技术寻找OVA12作用靶点，发现OVA12能负向调控抑癌基因p53表达，但OVA12是否会影响p53蛋白转录活性、是否调控突变型p53蛋白表达及调控p53蛋白表达机制等问题尚未解决。因此，本项目选取p53野生型和突变型细胞株，构建OVA12高表达和干扰细胞系，研究OVA12负向调控p53蛋白的生物学功能，并通过免疫共沉淀及蛋白芯片等技术探讨OVA12调控p53蛋白的作用机制。本项目研究具有重要的理论价值和良好的应用前景，能够为研发新的抗肿瘤靶向药物提供研究思路和作用靶点。

Identifying new tumor antigens and determining their roles and mechanism in tumorigenesis are critical to the development of molecular targeted therapy. Tumor antigen OVA12 was obtained from a human ovarian cancer cDNA library utilizing the approach of SEREX analysis, which is characteristically highly expressed in tumor cells and tissues. We have demonstrated that OVA12 played a notable role in accelerating tumor development both in vitro and in vivo. By using cDNA microarray analysis and protein 2 D gel electrophoresis combined with mass spectrometry, we found that OVA12 could negatively regulated the tumor suppressor gene p53. However, whether OVA12 affects p53 transcriptional activity? Whether OVA12 regulates the expression of mutant p53?What’s the mechanism by which OVA12 negatively regulates p53? Based on these, we will select the p53 wild type and mutant tumor cells, establish the stable over-expressed and knocking-down cancer cell lines and studying the biological function of OVA12 in regulating the p53 expression. Besides, we will explore to elucidate the mechanism by which OVA12 negatively regulates p53 by using Co-immunoprecipitation and protein microarray assay. We believe that the accomplishment of this project is of great theoretical significance and good prospect of application and will provide the research ideas and targets for the development of novel anticancer drug or biologics, which could be a novel breakthrough of tumor immunity field.