Molecular Mechanisms of Metastasis in Mammary Tumor Mod

描述（由申请人提供）：转移是肿瘤细胞从原发部位扩散到远处器官并建立继发性肿瘤的过程。由于转移难以检测和治愈，这些生长是约90%癌症死亡的原因。为了形成转移，肿瘤细胞需要通过周围组织侵入，渗入循环。在循环中移动后，存活的细胞外渗到远处，并建立新的恶性集落（二次生长）。阐明肿瘤转移机制的一个关键问题是转移的每个步骤是否需要不同的遗传或表观遗传变化。出于这个原因，识别负责编程这些变化的基因和基因产物并剖析它们的功能变得至关重要。 在这个建议中，小鼠乳腺肿瘤转移模型和人类乳腺肿瘤模型系统进行了研究，以寻找基因的多效性作用，转移级联的中央调节器。使用DNA微阵列技术，我们已经确定了几个候选基因，其表达与完成转移过程的特定步骤的能力密切相关。将在两种系统中进行详细的验证和表征，以了解这些基因在转移过程中的作用。对这些转移相关基因的研究将开辟大量的实验途径，并允许详细解剖这一多步骤过程的细胞和分子机制。

DESCRIPTION (provided by applicant): Metastasis is the process by which tumor cells spread from a primary site to distant organs and establish secondary tumors. Because metastases are difficult to detect and cure, these growths are the cause of approximately 90% of cancer mortafity. To form metastases, tumor cells need invade through the surrounding tissue, intravasate into the circulation. After traveling in the circulation, surviving cells extravasate into a distant site, and establish new malignant colonies (secondary growth). A key issue in elucidating the mechanisms of tumor metastasis is the question of whether distinct genetic or epigenetic changes are required for each of the individual steps of metastasis. For this reason, it has become crucial to identify the genes and gene products responsible for programming these changes and to dissect their functions. In this proposal, a mouse mammary tumor metastasis model and a human mammary tumor model system are investigated to search for genes that function as pleiotropically acting, central regulators of the metastatic cascade. Using DNA microarray technology, we have identified several candidate genes whose expression strongly correlates with the ability to accomplish specific steps of the metastatic process. Detailed validation and characterization will be performed in both systems to understand the roles these genes play in the metastatic process. Study of these metastasis-associated genes will open up a large number of experimental avenues and allow detailed dissection of the cellular and molecular mechanisms of this multi-step process.