Scata Kimberly A, El-Deiry Wafik S
University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA.
Adv Exp Med Biol. 2007;608:70-86. doi: 10.1007/978-0-387-74039-3_5.
The tumor suppressor genes p53 and BRCA1 are involved in hereditary as well as sporadic breast cancer development and therapeutic responses. While p53 mutations contribute to resistance to chemo- and radiotherapy, BRCA1 dysfunction leads to enhanced sensitivity to DNA damaging therapeutic agents. The biochemical pathways used by p53 and BRCA1 for signaling tumor suppression involve some cross-talk including repression of BRCA1 transcription by p53 and altered selectivity of p53-dependent gene activation by BRCA1. In this chapter we review clinical and preclinical data implicating p53 and BRCA1 in breast cancer chemosensitivity. We discuss the known signaling pathways downstream of p53 or BRCA1 that contribute to their modulation of therapeutic responses, and we discuss the implications of p53 or BRCA1 mutation in therapeutic design.
肿瘤抑制基因p53和BRCA1参与遗传性以及散发性乳腺癌的发生发展和治疗反应。p53突变会导致对化疗和放疗产生抗性，而BRCA1功能障碍则会导致对DNA损伤治疗药物的敏感性增强。p53和BRCA1用于肿瘤抑制信号传导的生化途径存在一些相互作用，包括p53对BRCA1转录的抑制以及BRCA1对p53依赖性基因激活选择性的改变。在本章中，我们综述了涉及p53和BRCA1与乳腺癌化疗敏感性相关的临床和临床前数据。我们讨论了p53或BRCA1下游已知的信号通路，这些通路有助于它们对治疗反应的调节，并且我们还讨论了p53或BRCA1突变在治疗设计中的意义。
