Subcellular localization of accumulated p53 in ovarian cancer cells
Subcellular localization of accumulated p53 in ovarian cancer cells
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DOI：
10.1006/gyno.1996.0137
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发表时间：
1996-05-01
影响因子：
4.7
通讯作者：
Kreienberg, R
中科院分区：
文献类型：
--
作者：
Runnebaum, IB;Kieback, DG;Kreienberg, R
肿瘤抑制基因p53的失活通常与卵巢癌有关。稳定的p53蛋白的积累是这种肿瘤类型的共同特征。p53核心区的潜在突变可导致正常构象状态的丧失或DNA结合和转录调控所需的残基的丧失。选择在我们实验室建立的5个无HPV的卵巢癌细胞系，其具有和不具有免疫细胞化学可检测的p53表达，以用于异常p53的亚细胞定位和基因突变类型的相关性。关于染色强度和积累p53的细胞的比例的表达水平的特征在于采用免疫反应性评分。两个细胞系的点错义突变的核心区域表现出强烈的核或核+胞质染色。一个细胞系与排他性染色的细胞质中含有一个删除的主要核定位信号。在没有p53积累的两个细胞系中，一个含有导致移码的微缺失，另一个携带野生型序列。MDM2癌基因未扩增，其基因产物未过表达。在卵巢癌中，失活的p53可根据潜在突变的类型在两个主要细胞区室中积累。(C)出版社：Academic Press，Inc.
Inactivation of the tumor suppressor gene p53 is frequently associated with ovarian cancer. Accumulation of stabilized p53 protein is a common feature in this tumor type. Underlying mutations in the p53 core region can lead to loss of the normal conformational state or loss of residues necessary for DNA binding and transcriptional regulation, Five HPV-free ovarian cancer cell lines established in our laboratory with and without immunocytochemically detectable p53 expression were selected for the correlation of subcellular localization of aberrant p53 and the type of gene mutation. The expression level regarding staining intensity and proportion of cells accumulating p53 was characterized employing an immunoreactive score. Two cell lines with point missense mutations in the core region showed strong nuclear or nuclear plus cytoplasmic staining. One cell line with exclusive staining of the cytoplasm contained a deletion of the major nuclear localization signal. Among two cell lines without p53 accumulation, one contained a microdeletion resulting in a frame shift, the other carried the wild-type sequence. The MDM2 oncogene was not amplified and its gene product was not overexpressed, In ovarian cancer, inactivated p53 can accumulate in both major cell compartments depending on the type of the underlying mutation. (C) 1996 Academic Press, Inc.