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

越来越多的证据表明，编码p73的基因，一种与原型肿瘤抑制因子p53同源的分子，在各种人类恶性肿瘤中不像p53那样经常发生突变。结合p73与p53的功能相似性，我们假设当肿瘤细胞的内在p73可以通过迄今未知的机制上调时，肿瘤细胞的生长可能受到控制。为了阐明这一机制，我们新制备了p73特异性抗体，并分析了一系列人体组织。结果表明，p73特异性定位于胸腺髓质上皮细胞的细胞核，而不是在皮质上皮细胞。此外，使用胸腺上皮细胞系的体外研究表明，p73可能参与调节M-CSF以及GM-CSF。众所周知，在髓质上皮中，培养树突状细胞和巨噬细胞，用于在该区域建立未成熟T细胞的阴性选择。因此，这意味着髓质中的p73可能具有重要的作用，以控制基质细胞的负选择。我们还调查了A。与我校海洋生物科学研究所合作，从天然资源的生物活性分子中特异性调控p73表达的分子。目前，我们已经找到了A。一定比例的Aristertoles。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，并发展其相关的方法，以控制肿瘤细胞周期，以及肿瘤免疫可能通过激活抗原提呈细胞。

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.