Sherr Charles J, McCormick Frank
Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Cancer Cell. 2002 Aug;2(2):103-12. doi: 10.1016/s1535-6108(02)00102-2.
The life history of cancer cells encompasses a series of genetic missteps in which normal cells are progressively transformed into tumor cells that invade surrounding tissues and become malignant. Most prominent among the regulators disrupted in cancer cells are two tumor suppressors, the retinoblastoma protein (RB) and the p53 transcription factor. Here, we discuss interconnecting signaling pathways controlled by RB and p53, attempting to explain their potentially universal involvement in the etiology of cancer. Pinpointing the various ways by which the functions of RB and p53 are subverted in individual tumors should provide a rational basis for developing more refined tumor-specific therapies.
癌细胞的生命历程包含一系列基因错误,在此过程中正常细胞逐渐转变为肿瘤细胞,这些肿瘤细胞会侵袭周围组织并变得具有恶性。在癌细胞中被破坏的调节因子中,最突出的是两种肿瘤抑制因子,即视网膜母细胞瘤蛋白(RB)和p53转录因子。在此,我们讨论由RB和p53控制的相互关联的信号通路,试图解释它们在癌症病因学中潜在的普遍作用。明确RB和p53的功能在个体肿瘤中被颠覆的各种方式,应该为开发更精确的肿瘤特异性疗法提供合理依据。