pp32 reduction induces differentiation of TSU-Pr1 cells
pp32 reduction induces differentiation of TSU-Pr1 cells
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DOI：
10.1016/s0002-9440(10)63117-3
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发表时间：
2004-01-01
影响因子：
6
通讯作者：
Pasternack, GR
中科院分区：
文献类型：
--
作者：
Brody, JR;Kadkol, SS;Pasternack, GR
pp32 (ANP32A) 是一种核磷蛋白，在自我更新细胞群和肿瘤细胞中以无突变形式表达。从机制上讲，PP32 可能作为抑制组蛋白乙酰化和调节即早期和细胞因子 mRNA 稳定性的单独复合物的一部分来调节分化过程中重要的途径。前列腺腺癌以分化相关的方式表达pp32——分化良好的肿瘤比分化差的肿瘤表达更低水平的PP32。在良性前列腺中，PP32 在基底细胞中表达，但在终末分化的腺细胞中不表达。基于这些观察，我们假设 pp32 表达的减少可能是一个重要的分化信号。我们使用反义 pp32 和 RNAi 转染来研究 TSU-Pr1 癌细胞系中 pp32 表达减少的影响。 pp32 减少诱导 Tsu-Pr1 细胞分化为神经元样细胞，并抑制生长。 pp32 的减少和随后的分化伴随着与 PP32 复合的 SET 表达的显着减少、组蛋白 114 乙酰化状态的显着变化以及分化途径中基因的进一步差异表达。因此，未分化的 TSU-Pr1 肿瘤细胞系中 PP32 的减少会诱导分化，因此可能是正常细胞和肿瘤细胞中分化控制途径的一个要素。
pp32 (ANP32A) is a nuclear phosphoprotein expressed as a nomnutated form in self-renewing cell populations and neoplastic cells. Mechanistically, PP32 may regulate pathways important in the process of differentiation as part of separate complexes inhibiting histone acetylation and regulating immediate-early and cytokine mRNA stability. Prostatic adenocarcinomas express pp32 in a differentiation related manner-well-differentiated tumors express lower levels of PP32 than poorly differentiated tumors. In benign prostate, PP32 is expressed in basal cells but not in terminally differentiated glandular cells. Based on these observations, we hypothesized that reduction of pp32 expression might be an important differentiation signal. We used antisense pp32 and RNAi transfection to study the effects of reduced pp32 expression in the TSU-Pr1 carcinoma cell line. pp32 reduction induced Tsu-Pr1 cells to differentiate into neuronal-like cells with associated inhibition of growth. Reduction of pp32 and consequent differentiation were accompanied by a marked reduction in expression of SET, which complexes with PP32, by a marked change in acetylation status of histone 114, and by further differential expression of genes in differentiation pathways. Thus, reduction of PP32 in the undifferentiated TSU-Pr1 neoplastic cell line induces differentiation and thus may be an element of a differentiation control pathway in both normal and neoplastic cells.