Restoration of growth arrest by p16INK4, p21WAF1, pRB, and p53 is dependent on the integrity of the endogenous cell-cycle control pathways in human glioblastoma cell lines
Restoration of growth arrest by p16INK4, p21WAF1, pRB, and p53 is dependent on the integrity of the endogenous cell-cycle control pathways in human glioblastoma cell lines
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DOI：
10.1006/excr.1997.3810
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发表时间：
1998-01-10
影响因子：
3.7
通讯作者：
Haas, M
中科院分区：
文献类型：
--
作者：
Costanzi-Strauss, E;Strauss, BE;Haas, M
本研究的目的是证明，在人多形性胶质母细胞瘤（GEM）细胞系的诱导生长停滞的逆转录病毒介导的转导的生长控制基因是依赖于特定的内源性控制途径的完整性。我们评估了内源性p16（INK4A），p21（CIP1），pRb，或p53基因在8个GEM系的状态。正如预期的那样，我们发现了各种基因缺陷的组合。用p16（INK4A）、p21（CIP1）、pRb或p53基因转导这些细胞系中的5个的结果是不完全可预测的。由编码pie的基因的转移介导的生长抑制作用依赖于pRb蛋白的存在，但与p53状态无关。p21是一种广泛活性的CDK抑制剂和生长停滞的强诱导剂，在分析的胶质母细胞瘤细胞系组中不是通用的生长抑制剂。编码pRb或p53的病毒对GEM细胞增殖的抑制通常是可预测的，并且似乎与pie或p21的状态无关。通过集落形成试验、观察形态学变化和台盼蓝拒染细胞活力染色评估细胞生长抑制。我们的研究结果表明，要完成这些细胞周期控制基因的转导抑制GEM细胞增殖，内源性细胞周期控制基因的状态必须考虑在内。(C)北京：科学出版社.
The aim of this study was to demonstrate that the induction of growth arrest in human glioblastoma multiforme (GEM) cell lines by retrovirus-mediated transduction of growth control genes was dependent upon the integrity of specific endogenous control pathways. We assessed the status of the endogenous p16(INK4A), p21(CIP1), pRb, or p53 genes in eight GEM lines. As expected, we found varied combinations of gene defects. The outcome of transducing five of these cell lines with p16(INK4A), p21(CIP1), pRb, or p53 genes was not entirely predictable, The growth-inhibitory effects mediated by the transfer of the gene encoding pie was dependent on the presence of the pRb protein, but was independent of p53 status. p21, a broadly active CDK inhibitor and a strong inducer of growth arrest, was not a universal growth suppressor in the group of glioblastoma cell lines analyzed. The suppression of GEM cell proliferation by viruses encoding pRb or p53 was generally predictable and appeared to be independent of the status of either pie or p21. Suppression of cell growth was assessed by a colony formation assay, by observance of alterations in morphology, and by cell viability staining for trypan blue exclusion. Our findings suggest that to accomplish the suppression of GEM cell proliferation by the transduction of these cell-cycle control genes, the status of endogenous cell-cycle control genes must be taken into account. (C) 1998 Academic Press.