{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(1)"],"submitter":["Dalmases A"],"pubmed_abstract":["NF-?B has been linked to doxorubicin resistance in breast cancer patients. NF-?B nuclear translocation and DNA binding in doxorubicin treated-breast cancer cells have been extensively examined; however its functional relevance at transcriptional level on NF-?B-dependent genes and the biological consequences are unclear. We studied NF-?B-dependent gene expression induced by doxorubicin in breast cancer cells and fresh human cancer specimens with different genetic backgrounds focusing on their p53 status. NF-?B-dependent signature of doxorubicin was identified by gene expression microarrays in breast cancer cells treated with doxorubicin and the IKK?-inhibitor MLN120B, and confirmed ex vivo in human cancer samples. The association with p53 was functionally validated. Finally, NF-?B activation and p53 status was determined in a cohort of breast cancer patients treated with adjuvant doxorubicin-based chemotherapy. Doxorubicin treatment in the p53-mutated MDA-MB-231 cells resulted in NF-?B driven-gene transcription signature. Modulation of genes related with invasion, metastasis and chemoresistance (ICAM-1, CXCL1, TNFAIP3, IL8) were confirmed in additional doxorubicin-treated cell lines and fresh primary human breast tumors. In both systems, p53-deficient background correlated with the activation of the NF-?B-dependent signature. Furthermore, restoration of p53WT in the mutant p53 MDA-MB-231 cells impaired NF-?B driven transcription induced by doxorubicin. Moreover, a p53 deficient background and nuclear NF-?B/p65 in breast cancer patients correlated with reduced disease free-survival. This study supports that p53 deficiency is necessary for a doxorubicin driven NF-?B-response that limits doxorubicin cytotoxicity in breast cancer and is linked to an aggressive clinical behavior."],"journal":["Oncotarget"],"pagination":["196-210"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3960201"],"repository":["biostudies-literature"],"pubmed_title":["Deficiency in p53 is required for doxorubicin induced transcriptional activation of NF-?B target genes in human breast cancer."],"pmcid":["PMC3960201"],"pubmed_authors":["Espinosa L","Albanell J","Tusquets I","Eroles P","Furriol J","Rovira A","Chamizo C","Bigas A","Rojo F","Gonzalez I","Rincon R","Arpi O","Menendez S","Servitja S","Dalmases A","Corominas JM","Lluch A"],"additional_accession":[]},"is_claimable":false,"name":"Deficiency in p53 is required for doxorubicin induced transcriptional activation of NF-?B target genes in human breast cancer.","description":"NF-?B has been linked to doxorubicin resistance in breast cancer patients. NF-?B nuclear translocation and DNA binding in doxorubicin treated-breast cancer cells have been extensively examined; however its functional relevance at transcriptional level on NF-?B-dependent genes and the biological consequences are unclear. We studied NF-?B-dependent gene expression induced by doxorubicin in breast cancer cells and fresh human cancer specimens with different genetic backgrounds focusing on their p53 status. NF-?B-dependent signature of doxorubicin was identified by gene expression microarrays in breast cancer cells treated with doxorubicin and the IKK?-inhibitor MLN120B, and confirmed ex vivo in human cancer samples. The association with p53 was functionally validated. Finally, NF-?B activation and p53 status was determined in a cohort of breast cancer patients treated with adjuvant doxorubicin-based chemotherapy. Doxorubicin treatment in the p53-mutated MDA-MB-231 cells resulted in NF-?B driven-gene transcription signature. Modulation of genes related with invasion, metastasis and chemoresistance (ICAM-1, CXCL1, TNFAIP3, IL8) were confirmed in additional doxorubicin-treated cell lines and fresh primary human breast tumors. In both systems, p53-deficient background correlated with the activation of the NF-?B-dependent signature. Furthermore, restoration of p53WT in the mutant p53 MDA-MB-231 cells impaired NF-?B driven transcription induced by doxorubicin. Moreover, a p53 deficient background and nuclear NF-?B/p65 in breast cancer patients correlated with reduced disease free-survival. This study supports that p53 deficiency is necessary for a doxorubicin driven NF-?B-response that limits doxorubicin cytotoxicity in breast cancer and is linked to an aggressive clinical behavior.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Jan","modification":"2021-02-20T19:29:14Z","creation":"2019-03-27T01:23:41Z"},"accession":"S-EPMC3960201","cross_references":{"pubmed":["24344116"],"doi":["10.18632/oncotarget.1556"]}}