title: Enhancement of vascular endothelial growth factor-mediated angiogenesis in tamoxifen-resistant breast cancer cells: role of Pin1 overexpression.
abstract: Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. Here, we found that TAM-resistant MCF-7 cells (TAMR-MCF-7 cells) produced higher levels of vascular endothelial growth factor (VEGF) than control MCF-7 cells. Molecular analyses using reporter genes and Western blots supported the involvement of c-Jun/activator protein-1 and hypoxia-inducible factor 1alpha in enhanced VEGF transcription in TAMR-MCF-7 cells. Pin1, a peptidyl prolyl isomerase, was consistently overexpressed in TAMR-MCF-7 cells, and c-Jun/activator protein-1-dependent VEGF transcription in TAMR-MCF-7 cells was almost completely inhibited by Pin1 siRNA and by the Pin1 inhibitor juglone. Chick chorioallantoic membrane assays confirmed that the increased angiogenic intensity of TAMR-MCF-7 cells was significantly suppressed by Pin1 inhibition. These results show that Pin1 overexpression is closely associated with VEGF-mediated angiogenesis and suggest that Pin1 is a potential therapeutic target of excessive angiogenesis in TAM-resistant breast cancer cases.
authors: BK21 Project Team, College of Pharmacy, Chosun University, Gwangju, South Korea.
authors: Mi Ra
authors: MR
authors: Kim
authors: Hong Seok
authors: HS
authors: Choi
authors: Jin Won
authors: JW
authors: Yang
authors: Byung Chul
authors: BC
authors: Park
authors: Jung-Ae
authors: JA
authors: Kim
authors: Keon Wook
authors: KW
authors: Kang
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000098:blood supply / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000235:genetics* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D018808:Transcription Factor AP-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D013629:Tamoxifen; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase