Rotter V, Aloni-Grinstein R, Schwartz D, Elkind N B, Simons A, Wolkowicz R, Lavigne M, Beserman P, Kapon A, Goldfinger N
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Semin Cancer Biol. 1994 Jun;5(3):229-36.
Inactivation of the p53 tumor suppressor gene plays a major role in malignant transformation. The central question in this issue is concerned with the understanding of the function of p53 in normal cells and its deregulation in cancer cells. Several in vitro and in vivo experimental models have indicated that induction of cells to undergo differentiation involve up-regulation in the expression of the p53. In the case of B cell differentiation, p53 was found to be involved in several steps of the differentiation pathway. The conclusion that p53 plays a role in normal development and differentiation in vivo is substantiated by the observation that p53 is expressed during embryonic development and is detected at low levels in a number of organs of adult mice. Accentuated levels of p53 in testes of adult mice, suggests that p53 plays a role in the meiotic process of spermatogenesis. B cell differentiation and spermatogenesis are biological pathways which normally involve DNA reshuffling and rearrangements. In accordance with the notion that p53 is associated with DNA repair it is tempting to speculate that at least in these physiological pathways p53 functions as a master gene that controls genome integrity.
p53肿瘤抑制基因的失活在恶性转化中起主要作用。这个问题的核心是对p53在正常细胞中的功能及其在癌细胞中的失调的理解。几个体外和体内实验模型表明，诱导细胞分化涉及p53表达的上调。在B细胞分化的情况下，发现p53参与分化途径的几个步骤。p53在体内正常发育和分化中起作用这一结论，通过观察到p53在胚胎发育期间表达且在成年小鼠的一些器官中低水平检测到而得到证实。成年小鼠睾丸中p53水平升高，表明p53在精子发生的减数分裂过程中起作用。B细胞分化和精子发生是通常涉及DNA重排和重新排列的生物学途径。根据p53与DNA修复相关的观点，很容易推测至少在这些生理途径中p53作为控制基因组完整性的主基因发挥作用。
