Department of Surgical Oncology, University Health Network, Ontario, Canada.
Adv Exp Med Biol. 2012;727:241-57. doi: 10.1007/978-1-4614-0899-4_18.
It has been more than two decades since Notch has been identified as an oncogene in mouse mammary tumor virus-infected mice. Since this discovery, activated Notch signaling and up-regulation of tumor-promoting Notch target genes have been observed in human breast cancer. In addition, high expression of Notch ligands and receptors has been shown to correlate with poor outcome in this malignancy. Notch affects multiple cellular processes including stem cell maintenance, cell fate specification, differentiation, proliferation, motility and survival. Perturbation of these activities is a hallmark of carcinogenesis and evidence continues to accumulate that aberrant Notch activity influences breast cancer progression through these processes.
自 Notch 被鉴定为感染鼠乳腺肿瘤病毒的小鼠中的致癌基因以来,已经过去了二十多年。自这一发现以来,在人类乳腺癌中观察到激活的 Notch 信号和促进肿瘤的 Notch 靶基因的上调。此外,研究表明,Notch 配体和受体的高表达与这种恶性肿瘤的不良预后相关。 Notch 影响多种细胞过程,包括干细胞维持、细胞命运特化、分化、增殖、迁移和存活。这些活动的紊乱是致癌作用的标志,越来越多的证据表明,异常的 Notch 活性通过这些过程影响乳腺癌的进展。