Molecular Mechanisms of Metastasis in Mammary Tumor Mod

描述（由申请人提供）：转移是指肿瘤细胞从原发部位扩散到远处器官并形成继发肿瘤的过程。由于转移难以发现和治愈，这些肿瘤的生长是大约90%的癌症死亡率的原因。为了形成转移，肿瘤细胞需要通过周围组织侵入，通过血管进入血液循环。在循环中行进后，存活的细胞外溢到远处，并建立新的恶性菌落（继发性生长）。阐明肿瘤转移机制的一个关键问题是转移的每个单独步骤是否需要不同的遗传或表观遗传变化。由于这个原因，识别负责编程这些变化的基因和基因产物并解剖它们的功能变得至关重要。

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.