Isaacs J S, Hardman R, Carman T A, Barrett J C, Weissman B E
UNC-Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA.
Cell Growth Differ. 1998 Jul;9(7):545-55.
Neuroblastoma (NB) cells in vitro are capable of bidirectional transdifferentiation, resulting in two distinct, yet reversible, phenotypes of neuroblastic (N-type) and nonneuronal (S-type) Schwann-like cells. Our previous studies suggested that the wild-type p53 protein is subject to differential regulation in a subset of neuronal cell types. To further test this hypothesis, we compared p53 function in three matched pairs of N- and S-type cell lines, each pair originating from an individual NB tumor. Our data show that although p53 remains cytoplasmically sequestered in a punctate pattern in N-type cells after DNA damage, the protein is diffusely distributed in the S-type cells and is additionally capable of translocating to the nucleus and mediating a biological response to this damage. Our data, therefore, suggest that the p53 protein may be differentially regulated by a neuronal cellular environment and that the sequestration of p53 in NB may be reversible.
体外培养的神经母细胞瘤(NB)细胞能够进行双向转分化,产生两种不同但可逆的表型:神经母细胞样(N型)和非神经元样(S型)雪旺氏样细胞。我们之前的研究表明,野生型p53蛋白在一部分神经元细胞类型中受到不同的调控。为了进一步验证这一假设,我们比较了三对匹配的N型和S型细胞系中的p53功能,每对细胞系均来源于单个NB肿瘤。我们的数据显示,虽然DNA损伤后p53在N型细胞中仍以点状模式被隔离在细胞质中,但该蛋白在S型细胞中呈弥漫性分布,并且还能够转运至细胞核并介导对这种损伤的生物学反应。因此,我们的数据表明p53蛋白可能受到神经元细胞环境的不同调控,并且p53在NB中的隔离可能是可逆的。