Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D
Mutant p53 in MDA-MB-231 breast cancer cells is stabilized by elevated phospholipase D activity and contributes to survival signals generated by phospholipase D
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DOI：
10.1038/sj.onc.1209735
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发表时间：
2006-11-01
期刊：
影响因子：
8
通讯作者：
Foster, D. A.
中科院分区：
文献类型：
--
作者：
Hui, L.;Zheng, Y.;Foster, D. A.
p53是人类癌症中最常见的突变基因。虽然肿瘤发生中p53的肿瘤抑制功能的丧失已经得到了很好的表征，但在大多数癌症中观察到的功能获得性p53突变并没有得到广泛的重视。人乳腺癌细胞系MDA-MB-231，其具有高水平的突变型p53，具有高水平的磷脂酶D（PLD）活性，当剥夺血清生长因子时，其在这些细胞中提供存活信号。我们在这里报告的突变p53在MDA-MB-231细胞中是稳定的PLD活性升高，在这些细胞。令人惊讶的是，缺乏血清的MDA-MB-231细胞的存活依赖于突变型p53。这些数据表明，突变的p53，稳定的PLD活性升高，可以有助于抑制人乳腺癌细胞系中的细胞凋亡，并建议在肿瘤发生的早期选择p53突变，以抑制新出现的肿瘤细胞凋亡的基本原理。
p53 is the most commonly mutated gene in human cancer. Although the loss of tumor suppressor functions for p53 in tumorigenesis is well characterized, gain-of-function p53 mutations observed in most cancers are not as widely appreciated. The human breast cancer cell line MDA-MB-231, which has high levels of a mutant p53, has high levels of phospholipase D (PLD) activity, which provides a survival signal in these cells when deprived of serum growth factors. We report here that the mutant p53 in MDA-MB-231 cells is stabilized by the elevated PLD activity in these cells. Surprisingly, the survival of MDA-MB-231 cells deprived of serum was dependent on the mutant p53. These data indicate that a mutant p53, stabilized by elevated PLD activity, can contribute to the suppression of apoptosis in a human breast cancer cell line and suggest a rationale for the selection of p53 mutations early in tumorigenesis to suppress apoptosis in an emerging tumor.