Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, People's Republic of China.
Mol Cell Biochem. 2011 Nov;357(1-2):415-22. doi: 10.1007/s11010-011-0912-4. Epub 2011 Jun 10.
In this study, in order to investigate the p53-independent function of p14ARF, we established p14ARF-inducible clones in the p53-deficient HCT cell line using the doxycycline-inducible expression system. A strong cell growth inhibition and G1/S arrest were observed after doxycycline induction in p53-/-HCT cells, and the cells also exhibited an obvious decrease of DNA synthesis. We further examined if the MEK/ERK pathway is involved in the G1 arrest induced by p14ARF in p53-/-HCT cells. The results indicate that ERK1/2 and p21 were activated upon p14ARF induction. Totally, the functional roles of ERK and p21 for ARF in p53-independent tumor suppression were demonstrated.
在这项研究中，为了研究 p14ARF 的 p53 非依赖性功能，我们使用强力霉素诱导表达系统在 p53 缺失的 HCT 细胞系中建立了 p14ARF 诱导克隆。在 p53-/-HCT 细胞中，强力霉素诱导后观察到强烈的细胞生长抑制和 G1/S 期阻滞，并且细胞的 DNA 合成也明显减少。我们进一步研究了 p14ARF 是否通过 MEK/ERK 通路诱导 p53-/-HCT 细胞的 G1 期阻滞。结果表明，p14ARF 诱导后 ERK1/2 和 p21 被激活。总之，这些结果证明了 ERK 和 p21 在 p53 非依赖性肿瘤抑制中的功能作用。
