The role of MDM2 and MDM4 in breast cancer development and prevention.
The role of MDM2 and MDM4 in breast cancer development and prevention.
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DOI：
10.1093/jmcb/mjx007
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发表时间：
2017-02-01
影响因子：
5.5
通讯作者：
Haupt Y
中科院分区：
文献类型：
--
作者：
Haupt S;Vijayakumaran R;Miranda PJ;Burgess A;Lim E;Haupt Y
乳腺癌的主要死因不是原发肿瘤，而是复发、耐药、转移的疾病。识别导致侵袭性癌症的因素为治疗提供了重要线索。对致癌物的固有防御取决于每个人的个体分子构成。这些反应的重要分子决定因素受小鼠双分钟(MDM)家族的控制：由MDM2和MDM4蛋白组成。在正常、健康的成人细胞中，MDM家族的功能是关键地调节测量的细胞对压力和随后的恢复的反应。MDM家族的正常功能对于正常的乳房发育至关重要，对保持基因组的保真度也是如此。MDM家族成员的最大特点是对主要的肿瘤抑制基因P53进行负调控，以调节应激反应。它们对其他细胞监管机构的影响正在显现。MDM家族蛋白水平的不适当升高与癌症发病率的增加高度相关。探索MDM家族成员作为癌症治疗的靶点对于设计量身定制的抗癌治疗是相关的，但成功的方法必须从战略上考虑对目标癌症和邻近健康细胞和组织的影响。这篇综述集中在关于MDM家族在正常和恶性乳腺细胞中的作用的最新发现。
The major cause of death from breast cancer is not the primary tumour, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defence against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute (MDM) family: comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery. Proper function of the MDM family is vital for normal breast development, but also for preserving genomic fidelity. The MDM family members are best characterized for their negative regulation of the major tumour suppressor p53 to modulate stress responses. Their impact on other cellular regulators is emerging. Inappropriately elevated protein levels of the MDM family are highly associated with an increased risk of cancer incidence. Exploration of the MDM family members as cancer therapeutic targets is relevant for designing tailored anti-cancer treatments, but successful approaches must strategically consider the impact on both the target cancer and adjacent healthy cells and tissues. This review focuses on recent findings pertaining to the role of the MDM family in normal and malignant breast cells.