BRCA1, PML and telomere maintenance

乳腺癌影响了大约十分之一的女性，因此是一个主要的健康问题。为了提高该病的诊断、治疗和预后，了解导致该病发生和发展的分子缺陷是至关重要的。过去二十年来，在这方面取得了重大进展，但仍有相当数量的问题悬而未决。例如，目前还不清楚哪些是导致这种疾病的最关键分子，因此哪些是治疗干预的最佳靶点。在这项提议中，我们的目标是研究两个分子。第一种基因被称为BRCA1，在乳腺癌的遗传易感性中尤为重要。第二种被称为PML，虽然最初被描述为与白血病相关的基因，但后来发现它与许多癌症有关。具体地说，我们的目标是调查PML和BRCA1共同工作以预防癌症的可能性，以及它们通过调节染色体末端即端粒来做到这一点的可能性。

Breast cancer affects approximately one in ten women and is therefore a major health problem. In order to improve the diagnosis, treatment and prognosis of this disease, it is critical to understand the molecular defects which contribute to disease initiation and progression. Over the last twenty years significant progress has been made in this regard, however there still remain a considerable number of unanswered questions. For example, it is not yet clear which are the most critical molecules contributing to this disease and thus which are the best targets for therapeutic intervention. In this proposal, we aim to study two molecules. The first is called BRCA1 and is particularly important in inherited susceptibility to breast cancer. The second is called PML and, although originally described as a leukaemia-associated gene, it has since been implicated in a number of cancers. Specifically, we aim to investigate the possibility that PML and BRCA1 work together to protect against cancer and that they do this by regulating the ends of chromosomes, that is, the telomeres.