In vivo role of LMO4 and isolation of an LMO4-containing proteosome in breast cancer

乳腺癌是影响女性的最常见癌症，每10人中就有1人罹患这种疾病。尽管乳腺癌的治疗在过去几年中有了很大的改善，但25%被诊断患有这种癌症的女性将死于这种疾病。癌症研究的一个主要目标是识别与肿瘤发展有关的基因，并确定它们在正常细胞和癌细胞中的确切作用。设计有效的癌症治疗抑制剂需要了解导致癌症的基因变化背后的基本分子和细胞生物学。我们研究的重点是了解驱动乳腺组织生长和分化的正常细胞机制，以及导致乳腺癌的那些变化。核调节蛋白与许多不同类型的癌症和白血病有关。我们的目标是识别乳腺组织中的关键调节因子，表征它们的结构特性和生物学作用，最终了解它们是如何将正常细胞转移到癌细胞的。这项建议的核心是一个特定的调控分子的特征，我们最近证明，在56%的人类原发乳腺癌和38%的浸润性导管原位癌中过表达。这些研究将包括确定其正常的生物学功能，以及确定该调节因子与乳腺癌细胞中的蛋白质相关。

Breast cancer is the most common cancer to affect women, with one in 10 developing the disease. Although treatment of breast cancer has substantially improved over the last few years, 25% of women diagnosed with this cancer will die from the disease. A major objective of cancer research is the identification of genes involved in tumour development and definition of their precise role in both normal and cancer cells. The design of effective therapeutic inhibitors of cancer requires an understanding of the basic molecular and cellular biology behind the genetic changes thought to contribute to cancer. The focus of our research is to understand normal cellular mechanisms that drive growth and differentiation of breast tissue, and those changes that lead to breast cancer. Nuclear regulatory proteins have been implicated in many different types of cancers and leukaemias. We aim to identify the key regulators in breast tissue, characterising both their structural properties and biological roles, with the ultimate view of understanding how they divert a normal cell to a cancerous cell. This proposal centres on the characterisation of a specific regulatory molecule which we recently demonstrated to be overexpressed in 56% of human primary breast cancers and in 38% of pre-invasive ductal carcinoma in situ. These studies will include defining its normal biologic function and identification of the proteins that this regulator associates with in breast cancer cells.