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的基因是一种与原型抑癌基因p53同源的分子，它知道在各种人类恶性肿瘤中不同于p53的罕见突变。结合p73和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，我们新制造了针对p73的抗体，并对一系列人体组织进行了分析。结果表明，p73仅定位于胸腺髓质上皮细胞的胞核，而不定位于皮质上皮细胞。此外，使用胸腺上皮细胞系进行的体外研究表明，p73可能参与了M-CSF和GM-CSF的调节。众所周知，在髓上皮细胞中培养树突状细胞和巨噬细胞，以建立该区域未成熟T细胞的负选择。因此，这些提示延髓中的p73可能具有控制基质细胞进行负选择的重要作用。我们还与我校海洋生物科学研究所合作，研究了一种特定调控自然资源中生物活性分子p73表达的分子。目前，我们已经发现了A的某一小部分。海胆具有上调人类胸腺上皮细胞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学，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。

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.