Cell Growth Control by Regulating the Expression of p73 : the Basics and Development of New Clinical Applications

通过调节 p73 表达来控制细胞生长：新临床应用的基础知识和开发

• 批准号: 13670182
• 负责人: ICHIMIYA Shingo
• 金额: $ 2.18万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670182/
• 关键词: p73; p53; cell cycle; thymic epithelial cell; immune regulation; p53ファミリー

Accumulating evidence has demonstrated that the gene encoding p73, a molecule homologous to the archetypal tumor suppressor p53, knows infrequent mutation in various human malignancies unlike p53. Together with functional similarities of p73 to p53, we hypothesized that tumor cell growth might be controlled when an intrinsic p73 of tumor cells could be up-regulated by hitherto unknown mechanism. To elucidate the mechanism, we have newly made antibodies specific to p73 and analyzed a series of human tissues. Results indicated that p73 was specifically localized at the nuclei of thymic medullary epithelial cells, but not in cortical epithelium. Moreover, in vitro studies using thymic epithelial cell lines showed that p73 was potentially involved regulation of M-CSF as well as GM-CSF. It is well known that in medullary epithelium foster dendritic cells and macrophages for establishing negative selection of immature T cells in the region. Thus, these imply that p73 in the medulla might have important roles, to control stromal cells for negative selection. We also investigated a. molecule specifically regulating the expression of p73 from biologically active molecules of natural resources in collaboration with the Institute of Marine Bioscience of our university. Currently, we have found a. certain fraction of the Aristertoles of. sea urchin has a capacity to up-regulating p73 of human thymic epithelial cells. We would like to further clarify the expression mechanism of p73 and develop its related methodology for controlling tumor cell cycle as well as tumor immunity possibly through the activation of antigen presenting cells.

越来越多的证据表明，编码p73的基因是一种与原型肿瘤抑制因子p53同源的分子，与p53不同，它在各种人类恶性肿瘤中很少发生突变。结合p73与p53的功能相似性，我们假设肿瘤细胞的内在p73可能通过未知的机制上调，从而控制肿瘤细胞的生长。为了阐明其机制，我们新制备了针对p73的抗体，并对一系列人体组织进行了分析。结果表明p73特异性定位于胸腺髓上皮细胞核，而不定位于皮质上皮细胞。此外，胸腺上皮细胞系的体外研究表明，p73可能参与M-CSF和GM-CSF的调节。众所周知，在髓上皮中培养树突状细胞和巨噬细胞可在该区域建立未成熟T细胞的负选择。因此，这暗示髓质中的p73可能在控制基质细胞负选择方面发挥重要作用。我们还与我校海洋生物科学研究所合作，从自然资源的生物活性分子中研究了一种特异性调节p73表达的分子。目前，我们已经找到了亚里士多德理论的一部分。海胆具有上调人胸腺上皮细胞p73的能力。我们希望进一步阐明p73的表达机制，并开发其相关方法，可能通过激活抗原提呈细胞来控制肿瘤细胞周期和肿瘤免疫。

项目成果

Momota H, Ichimiya S, Ikeda T, et al.: "Immunohistochemical analysis of the p53 family members in human craniopharyngiomas"Brain Tumor Pathology. 20. 311-315 (2003)

Momota H、Ichimiya S、Ikeda T 等人：“人颅咽管瘤中 p53 家族成员的免疫组织化学分析”脑肿瘤病理学。

Momota H, Ichimiya S, Kondo N, et al.: "Histone H2AX sensitizes glioma cells to genotoxic stimuli by recruiting DNA double-strand break repair proteins"International Journal of Oncology. 23・2. 311-315 (2003)

Momota H、Ichimiya S、Kondo N 等人：“组蛋白 H2AX 通过招募 DNA 双链断裂修复蛋白使神经胶质瘤细胞敏感”，《国际肿瘤学杂志》23・2（2003 年）。

Ichimiya S, Kojima T, Momota H, et al.: "p73 is expressed in human thymic epithelial cells"Journal of Histochemistry and Cytochemistry. 50. 455-462 (2002)

Ichimiya S、Kojima T、Momota H 等人：“p73 在人胸腺上皮细胞中表达”Journal of Histochemistry and Cytochemistry。

Ichimiya S, Kojima T, Momota H, et al.: "p73 is expressed in human thymic epithelial cells."Journal of Histochemistry and Cytochemistry. 50. 455-462 (2002)

Ichimiya S、Kojima T、Momota H 等人：“p73 在人胸腺上皮细胞中表达。”组织化学和细胞化学杂志。

Ichimiya S, Kojima T, Momota H, et al.: "p73 is expressed in human thymic epithelial cells"Journal of Histochemistry and Cytochemistry. 50・4. 455-462 (2002)

Ichimiya S、Kojima T、Momota H 等：“p73 在人胸腺上皮细胞中表达”Journal of Histochemistry and Cytochemistry 50・4 (2002)。