title: Regulation of the MDR1 promoter by E2F1 and EAPP.
abstract: Multidrug resistance (MDR), one of the main reasons for diminishing efficacy of prolonged chemotherapy, is frequently caused by the elevated expression of the ABCB1/MDR1 gene encoding PGP (P-glycoprotein). EAPP (E2F Associated PhosphoProtein) is a frequently overexpressed protein in human tumor cells. It inhibits apoptosis in a p21-dependent manner. We show here that EAPP stimulates the MDR1 promoter resulting in higher PGP levels. Independently of EAPP, E2F1 also increases the activity of the MDR1 promoter. Co-expression of pRb inhibits E2F1-, but not EAPP-dependent promoter activation. The upregulation of PGP might contribute to the survival of tumor cells during chemotherapy and worsen the prognosis for the patient.
authors.affiliation: Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, A-1030 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Andorfer
authors.forename: Hans
authors.initials: H
authors.lastname: Rotheneder
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D050687:E2F1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D016160:Retinoblastoma Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C503749:EAPP protein, human; D016160:Retinoblastoma Protein; D014157:Transcription Factors; D005047:Etoposide