Kumari Ratna, Chouhan Surbhi, Singh Snahlata, Chhipa Rishi Raj, Ajay Amrendra Kumar, Bhat Manoj Kumar
National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
J Biosci. 2017 Mar;42(1):31-41. doi: 10.1007/s12038-017-9667-8.
The tumour suppressor gene p53 is mutated in approximately 50% of the human cancers. p53 is involved in genotoxic stress-induced cellular responses. The role of EGFR and ERK in DNA-damage-induced apoptosis is well known. We investigated the involvement of activation of ERK signalling as a consequence of non-functional p53, in sensitivity of cells to doxorubicin. We performed cell survival assays in cancer cell lines with varying p53 status: MCF-7 (wild-type p53, WTp53), MDA MB-468 (mutant p53, MUTp53), H1299 (absence of p53, NULLp53) and an isogenic cell line MCF-7As (WTp53 abrogated). Our results indicate that enhanced chemosensitivity of cells lacking wild-type p53 function is because of elevated levels of EGFR which activates ERK. Additionally, we noted that independent of p53 status, pERK contributes to doxorubicin-induced cell death.
肿瘤抑制基因p53在大约50%的人类癌症中发生突变。p53参与基因毒性应激诱导的细胞反应。表皮生长因子受体（EGFR）和细胞外信号调节激酶（ERK）在DNA损伤诱导的细胞凋亡中的作用已为人所知。我们研究了由于p53功能缺失导致的ERK信号激活在细胞对多柔比星敏感性中的作用。我们在具有不同p53状态的癌细胞系中进行了细胞存活分析：MCF-7（野生型p53，WTp53）、MDA MB-468（突变型p53，MUTp53）、H1299（无p53，NULLp53）以及同基因细胞系MCF-7As（野生型p53缺失）。我们的结果表明，缺乏野生型p53功能的细胞化疗敏感性增强是由于激活ERK的EGFR水平升高所致。此外，我们注意到，与p53状态无关，磷酸化ERK（pERK）会导致多柔比星诱导的细胞死亡。
