Rose S L, Buller R E
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Minerva Ginecol. 2002 Jun;54(3):201-9.
Ovarian cancer remains the most deadly gynecologic malignancy, resulting in an estimated 23,300 new cases and 13,900 deaths in the United States in the year 2002. The discovery of the BRCA1 gene in 1994 has proven to be of great interest to the study of hereditary ovarian cancer. BRCA1 gene mutation confers a 16-42% lifetime risk of the development of ovarian cancer in those affected. Although BRCA1 functions as a tumor suppressor gene, conflicting studies have shown that BRCA1 dysfunction alone may not be sufficient for tumorigenesis. p53 is a tumor suppressor gene found to be dysfunctional in nearly 50% of all human cancers and in up to 80% of ovarian malignancies. The p53 protein product plays a crucial role in DNA surveillance and repair at the Gap 1-synthesis (G1-S) cell cycle checkpoint. Studies exhibiting the interaction of BRCA1 and p53 and the role of this interaction in DNA damage response led many investigators to suggest that p53 gene mutation is required for BRCA1-associated tumor development. This review explores the evidence for BRCA1 and p53 interplay, and outlines the crucial role p53 may play in BRCA1-related ovarian cancer.
卵巢癌仍然是最致命的妇科恶性肿瘤，2002年在美国估计有23300例新发病例和13900例死亡病例。1994年BRCA1基因的发现已被证明对遗传性卵巢癌的研究具有重大意义。BRCA1基因突变使受影响者一生中患卵巢癌的风险为16%至42%。尽管BRCA1作为一种肿瘤抑制基因发挥作用，但相互矛盾的研究表明，仅BRCA1功能障碍可能不足以引发肿瘤发生。p53是一种肿瘤抑制基因，在近50%的人类癌症以及高达80%的卵巢恶性肿瘤中被发现功能异常。p53蛋白产物在DNA监测以及在G1期向S期（G1-S）细胞周期检查点的修复过程中起着关键作用。显示BRCA1与p53相互作用以及这种相互作用在DNA损伤反应中的作用的研究，使得许多研究人员认为p53基因突变是BRCA1相关肿瘤发生所必需的。这篇综述探讨了BRCA1与p53相互作用的证据，并概述了p53在BRCA1相关卵巢癌中可能发挥的关键作用。
