STRESS RESPONSES IN MAMMALIAN CELLS

描述：血管生成对肿瘤生长至关重要，人们普遍认为 成为肿瘤转移的一个因素。福克曼和他的新近工作 同事们已经证明，抑制血管生成可以保持休眠状态 不断增长的微转移。大多数关于肿瘤血管生成的工作都有 重点是如何预防肿瘤的生长和转移，而不是针对什么 细胞和环境机制都参与了这一过程。 由细胞的微观或宏观环境的改变引起的压力 (例如，辐射、高温、缺氧和饥饿)已为人所知 触发高度复杂的细胞应激管理系统 好几年了。最近来自我们实验室的证据也表明，在 除了众所周知的应激蛋白外，环境应激还可以诱导 碱性成纤维细胞生长因子等生长因子的合成 (碱性成纤维生长因子)。这些血管生成蛋白在体外诱导的观察 这些情况可能会对以下进程产生重大影响 肿瘤发生学。一旦肿瘤发生，实体肿瘤 细胞必须促进新血管的形成，以提供营养 和氧气；否则，它们不能超过非常小的尺寸。因此， 防止新血管的形成一直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。这是众所周知的 新血管的生长是由血管生成因子刺激的。我们 提出血管生成因子，即碱性成纤维细胞生长因子可以由环境诱导 应激，如热休克、辐射、低血糖和缺氧。 环境压力会激活特殊的转录因子，它们是 称为激活蛋白-1(AP-1)。AP-1因子组成 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)。这个 活化的AP-1因子结合碱性成纤维细胞生长因子基因的调控区，从而 触发基因表达。此外，AP-1因子与其他因子协同作用 Ets-1蛋白等调控因子对bFGF基因的调控 表情。我们认为，调查AP-1因子的参与 通过对碱性成纤维细胞生长因子基因调控的研究，将有助于深入了解其作用机制。 应激诱导的肿瘤生长和转移也在分子水平上 使我们能够提高临床治疗的疗效。

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.