Pub. Date : 2011 Jun
PMID : 21518729
10 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | ATM and p53 regulate FOXM1 expression via E2F in breast cancer epirubicin treatment and resistance. | Epirubicin | forkhead box M1 | Homo sapiens |
| 2 | In this report, we investigated the role and regulation of forkhead box M1 (FOXM1) in breast cancer and epirubicin resistance. | Epirubicin | forkhead box M1 | Homo sapiens |
| 3 | We generated epirubicin-resistant MCF-7 breast carcinoma (MCF-7-EPI(R)) cells and found FOXM1 protein levels to be higher in MCF-7-EPI(R) than in MCF-7 cells and that FOXM1 expression is downregulated by epirubicin in MCF-7 but not in MCF-7-EPI(R) cells. | Epirubicin | forkhead box M1 | Homo sapiens |
| 4 | We generated epirubicin-resistant MCF-7 breast carcinoma (MCF-7-EPI(R)) cells and found FOXM1 protein levels to be higher in MCF-7-EPI(R) than in MCF-7 cells and that FOXM1 expression is downregulated by epirubicin in MCF-7 but not in MCF-7-EPI(R) cells. | Epirubicin | forkhead box M1 | Homo sapiens |
| 5 | We generated epirubicin-resistant MCF-7 breast carcinoma (MCF-7-EPI(R)) cells and found FOXM1 protein levels to be higher in MCF-7-EPI(R) than in MCF-7 cells and that FOXM1 expression is downregulated by epirubicin in MCF-7 but not in MCF-7-EPI(R) cells. | Epirubicin | forkhead box M1 | Homo sapiens |
| 6 | We also established that there is a loss of p53 function in MCF-7-EPI(R) cells and that epirubicin represses FOXM1 expression at transcription and gene promoter levels through activation of p53 and repression of E2F activity in MCF-7 cells. | Epirubicin | forkhead box M1 | Homo sapiens |
| 7 | Moreover, transient promoter transfection assays showed that epirubicin and its cellular effectors p53 and E2F1 modulate FOXM1 transcription through an E2F-binding site located within the proximal promoter region. | Epirubicin | forkhead box M1 | Homo sapiens |
| 8 | Chromatin immunoprecipitation analysis also revealed that epirubicin treatment increases pRB (retinoblastoma protein) and decreases E2F1 recruitment to the FOXM1 promoter region containing the E2F site. | Epirubicin | forkhead box M1 | Homo sapiens |
| 9 | We also found ataxia-telangiectasia mutated (ATM) protein and mRNA to be overexpressed in the resistant MCF-7-EPI(R) cells compared with MCF-7 cells and that epirubicin could activate ATM to promote E2F activity and FOXM1 expression. | Epirubicin | forkhead box M1 | Homo sapiens |
| 10 | In summary, our data show that ATM and p53 coordinately regulate FOXM1 via E2F to modulate epirubicin response and resistance in breast cancer. | Epirubicin | forkhead box M1 | Homo sapiens |