title: Constitutively activated ERK sensitizes cancer cells to doxorubicin: Involvement of p53-EGFR-ERK pathway.
abstract: 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.
authors.affiliation: National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
authors.forename: Ratna
authors.initials: R
authors.lastname: Kumari
authors.forename: Surbhi
authors.initials: S
authors.lastname: Chouhan
authors.forename: Snahlata
authors.initials: S
authors.lastname: Singh
authors.forename: Rishi Raj
authors.initials: RR
authors.lastname: Chhipa
authors.forename: Amrendra Kumar
authors.initials: AK
authors.lastname: Ajay
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Bhat
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C512478:EGFR protein, human; D066246:ErbB Receptors