Constitutively activated ERK sensitizes cancer cells to doxorubicin: Involvement of p53-EGFR-ERK pathway

Journal of biosciences

RATNA KUMARI¹  MANOJ KUMAR BHAT1¹  RISHI RAJ CHHIPA¹  SURBHI CHOUHAN¹  SNAHLATA SINGH¹  AMRENDRA KUMAR AJAY¹ 

[1] National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India$$

关键词: Doxorubicin;    EGFR;    ERK;    p53;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

The tumour suppressor gene p53 is mutated in approximately 50% of the human cancers. p53 is involved in genotoxicstress-induced cellular responses. The role of EGFR and ERK in DNA-damage-induced apoptosis is well known. Weinvestigated the involvement of activation of ERK signalling as a consequence of non-functional p53, in sensitivity ofcells to doxorubicin. We performed cell survival assays in cancer cell lines with varying p53 status: MCF-7 (wild-typep53, WTp53), MDA MB-468 (mutant p53, MUTp53), H1299 (absence of p53, NULLp53) and an isogenic cell lineMCF-7As (WTp53 abrogated). Our results indicate that enhanced chemosensitivity of cells lacking wild-type p53function is because of elevated levels of EGFR which activates ERK. Additionally, we noted that independent of p53status, pERK contributes to doxorubicin-induced cell death.

【 授权许可】

Unknown