BRCA1, PML and telomere maintenance

乳腺癌影响大约十分之一的妇女，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，了解导致疾病发生和进展的分子缺陷至关重要。在过去的二十年里，在这方面取得了重大进展，但仍然有相当多的问题没有得到回答。例如，目前尚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。在这个计划中，我们的目标是研究两个分子。第一种称为BRCA1，在遗传性乳腺癌易感性中特别重要。第二个基因被称为PML，尽管最初被描述为白血病相关基因，但它已与许多癌症有关。具体来说，我们的目标是研究PML和BRCA1共同作用以预防癌症的可能性，并且它们通过调节染色体的末端，即端粒来实现这一点。

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.