STRESS RESPONSES IN MAMMALIAN CELLS

描述：血管生成对肿瘤生长至关重要， 是肿瘤转移的一个因素。 Folkman和他的同事最近的工作 他的同事已经证明，抑制血管生成可以保持休眠状态， 生长中的微小转移 大多数关于肿瘤血管生成的研究 专注于如何预防肿瘤的生长和转移，而不是在什么 细胞和环境的机制都参与了这一过程。 由细胞的微环境或宏观环境改变引起的应激 (e.g.辐射，高温，缺氧和饥饿）已经被人们所知 触发高度复杂的细胞压力管理系统， 年 我们的实验室最近的证据也表明， 除了众所周知的应激蛋白外，环境应激还可以诱导 生长因子如碱性成纤维细胞生长因子合成 （bFGF）。 这些血管生成蛋白的诱导作用的观察， 这些情况可能会对这一进程产生重大影响， 肿瘤发生 一旦肿瘤发生，实体瘤 细胞必须促进新血管的形成以提供营养 和氧气;否则，它们不能生长超过非常小的尺寸。 因此，在本发明中， 防止新血管的形成是一种很有前途的新方法， 治疗癌症患者。 为了抑制新血管的生长，我们 需要了解肿瘤血管形成的机制。 已知 新血管的生长受到血管生成因子的刺激。 我们 提出血管生成因子，即，bFGF可被环境诱导 应激，如热休克、辐射、低血糖和缺氧。 环境压力激活特殊的转录因子， 称为活化蛋白-1（AP-1）。 AP-1因子由 在三个Jun家族成员（C-Jun，Jun B， Jun D和四个Fos家族成员（c-Fos、Fos B、Fra-1和Fra-2）。 的 激活的AP-1因子结合BFGF基因的调节区，然后 触发基因表达。 此外，AP-1因子与其他因子合作， 调节因子如Ets-1蛋白，用于调节bFGF基因 表情 我们认为，研究AP-1因子的参与， 在bFGF基因调控中的作用将为理解 压力诱导的肿瘤生长和转移在分子水平上 使我们能够提高临床治疗的效果。

DESCRIPTION: Angiogenesis is vital for tumor growth and is widely believed to be a factor in tumor metastasis. Recent work by Folkman and his colleagues has demonstrated that inhibition of angiogenesis can keep dormant micro-metastases from growing. Most work on angiogenesis in tumors has focused on how to preven tumor growth and metastasis and not at what mechanisms, both cellular and environmental, are involved in the process. Stress caused by alteration of the micro- or macroenvironment of a cell (e.g. radiation, high temperature, hypoxia, and starvation) has been known to trigger the highly complex cellular stress management system for many years. Recent evidence from our laboratories has also shown that, in addition to the well-known stress proteins, environmental stress can induce the synthesis of growth factor such as basic fibroblast growth factor (bFGF). The observation of the induction of these angiogenic proteins under these circumstances could have significant implications on the process of tumorigenesis. Once the tumor initiation has occurred, the solid tumor cells must promote the formation of new blood vessel to provide nutrients and oxygen; otherwise, they can not grow beyond a very small size. Thus, preventing the formation of new vessels has been a promising new approach to treat cancer patients. In order to inhibit the growth of new vessels, we need to understand the mechanisms of tumor vascularization. It is known that the growth of new vessels is stimulated by angiogenic factors. We proposed that angiogenic factors, i.e., bFGF can be induced by environmental stresses such as heat shock, radiation, hypoglycemia, and hypoxia. Environmental stresses activate special transcription factors, which are referred to as activating protein-1 (AP-1). The AP-1 factors are composed of dimeric complexes formed between three Jun family members (C-Jun, Jun B, Jun D and four Fos family members (c-Fos, Fos B, Fra-1, and Fra-2). The activated AP-1 factors bind the regulatory region of BFGF gene, which then triggers the gene expression. Moreover, AP-1 factors cooperate with other regulatory factor such as Ets-1 protein for the regulation of bFGF gene expression. We believe that investigating the involvement of AP-1 factors in bFGF gene regulation wil provide insight into understanding the mechanism of stress-induced tumor growt and metastasis at the molecular level as well as enable us to improve the efficacy of clinical therapy.