NEGATIVE GROWTH-REGULATION IN A GLIOBLASTOMA TUMOR-CELL LINE THAT CONDITIONALLY EXPRESSES HUMAN WILD-TYPE P53
NEGATIVE GROWTH-REGULATION IN A GLIOBLASTOMA TUMOR-CELL LINE THAT CONDITIONALLY EXPRESSES HUMAN WILD-TYPE P53
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DOI：
10.1073/pnas.87.16.6166
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发表时间：
1990-08-01
影响因子：
11.1
通讯作者：
ULLRICH, SJ
中科院分区：
文献类型：
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作者：
MERCER, WE;SHIELDS, MT;ULLRICH, SJ
为了研究人类野生型p53 （wt-p53）表达对细胞增殖的影响，我们构建了重组质粒pM47，其中wt-p53 cDNA受激素诱导的小鼠乳腺肿瘤病毒启动子转录控制，该启动子与显性生化选择标记基因Eco gpt相关。将pM47质粒导入人胶质母细胞瘤多形性肿瘤的T98G细胞中，获得稳定的克隆细胞系GM47.23，该细胞系在地塞米松暴露后有条件地表达wt-p53。我们发现，在呈指数增长的细胞中诱导wt-p53表达可抑制细胞周期进程，并且在去除诱导剂或感染猿猴病毒40后，抑制作用是可逆的。此外，当生长停滞的细胞被刺激增殖时，诱导wt-p53表达会抑制G0/G1期进入S期，细胞积累的DNA含量相当于细胞周期G0/G1期停滞的细胞。综上所述，这些研究表明，wt-p53可能在生长调节中起负作用。
To investigate the effect that human wild-type p53 (wt-p53) expression has on cell proliferation we constructed a recombinant plasmid, pM47, in which wt-p53 cDNA is under transcriptional control of the hormone-inducible mouse mammary tumor virus promoter linked to the dominant biochemical selection marker gene Eco gpt. The pM47 plasmid was introduced into T98G cells derived from a human glioblastoma multiforme tumor, and a stable clonal cell line, GM47.23, was derived that conditionally expressed wt-p53 following exposure to dexamethasone. We show that induction of wt-p53 expression in exponentially growing cells inhibits cell cycle progression and that the inhibitory effect is reversible upon removal of the inducer or infection with simian virus 40. Moreover, when growth-arrested cells are stimulated to proliferate, induction of wt-p53 expression inhibits G0/G1 progression into S phase and the cells accumulate with a DNA content equivalent to cells arrested in the G0/G1 phase of the cell cycle. Taken together, these studies suggest that wt-p53 may play a negative role in growth regulation.