title: Survivin transcription is associated with P-glycoprotein/MDR1 overexpression in the multidrug resistance of MCF-7 breast cancer cells.
abstract: Breast carcinoma is the most common malignancy in women. The progression of tumor is associated with overexpression of inhibitors of apoptosis proteins (IAPs) such as survivin and multidrug resistant P-glycoprotein (P-gp). PI3K/Akt pathway is involved in cell cycle progression, apoptosis and neoplastic transformation. PI3K/Akt has been shown to regulate survivin in breast cancer. The aim of this study was to investigate the expression of survivin and P-gp, the modulation of survivin by P-gp in PI3K/Akt during the progression of drug resistance (MDR) in MCF-7 breast cancer cells and adriamycin (ADR)-resistant MCF-7/ADR cells. The expression of survivin and P-gp in MCF-7/ADR cells were higher than that of the MCF-7 cells using RT-PCR and Western blot analysis. Survivin transcription was associated with P-glycoprotein/MDR1 overexpression using promoter activity analysis. LY294002, specific inhibitor of PI3K could suppress survivin and P-gp expression, decreased survivin promoter activity and enhanced cell sensitivity to drugs. This study shows survivin transcription was associated with P-glycoprotein/MDR1 overexpression, PI3k/Akt pathway was involved in P-glycoprotein/MDR1 associated survivin transcription activity in the multidrug resistant MCF-7 breast cancer cells.
authors.affiliation: The Key Laboratory of Chemical Biology, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Shiying
authors.initials: S
authors.lastname: Liu
authors.forename: Shengnan
authors.initials: S
authors.lastname: He
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xie
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zu
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000077022:Survivin; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002867:Chromones; D004317:Doxorubicin; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D000077022:Survivin; D014700:Verapamil; C513055:ABCB1 protein, human; C107489:BIRC5 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one