Estrogen-Dependent Dynamic Profile of eNOS-DNA Associations in Prostate Cancer (Articolo in rivista)

Type
Label
  • Estrogen-Dependent Dynamic Profile of eNOS-DNA Associations in Prostate Cancer (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1371/journal.pone.0062522 (literal)
Alternative label
  • Nanni Simona1,2; Aiello Aurora2,3; Re Agnese2, 4; Guffanti Alessandro5; Benvenuti Valentina3; Colussi Claudia2,3; Castro-Vega Luis Jaime6; Felsani Armando3, 5; Londono-Vallejo Arturo6; Capogrossi Maurizio C.7; Bacchetti Silvia1; Gaetano Carlo8; Pontecorvi Alfredo2; Farsetti Antonella1,3 (2013)
    Estrogen-Dependent Dynamic Profile of eNOS-DNA Associations in Prostate Cancer
    in PloS one
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Nanni Simona1,2; Aiello Aurora2,3; Re Agnese2, 4; Guffanti Alessandro5; Benvenuti Valentina3; Colussi Claudia2,3; Castro-Vega Luis Jaime6; Felsani Armando3, 5; Londono-Vallejo Arturo6; Capogrossi Maurizio C.7; Bacchetti Silvia1; Gaetano Carlo8; Pontecorvi Alfredo2; Farsetti Antonella1,3 (literal)
Pagina inizio
  • e62522 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 8 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 5 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1 Department of Experimental Oncology, National Cancer Institute Regina Elena, Rome, Italy. 2 Medical Pathology Institute, Catholic University, Rome, Italy. 3 Institute of Cell Biology and Neurobiology, National Research Council (CNR), Rome, Italy. 4 University of Messina, Messina, Italy 5 Genomnia srl, Lainate, Milan, Italy. 6 Institut Curie, Paris, France. 7 Istituto Dermopatico dell'Immacolata, Rome, Italy. 8 Goethe University, Frankfurt, Germany. (literal)
Titolo
  • Estrogen-Dependent Dynamic Profile of eNOS-DNA Associations in Prostate Cancer (literal)
Abstract
  • In previous work we have documented the nuclear translocation of endothelial NOS (eNOS) and its participation in combinatorial complexes with Estrogen Receptor Beta (ER?) and Hypoxia Inducible Factors (HIFs) that determine localized chromatin remodeling in response to estrogen (E2) and hypoxia stimuli, resulting in transcriptional regulation of genes associated with adverse prognosis in prostate cancer (PCa). To explore the role of nuclear eNOS in the acquisition of aggressive phenotype in PCa, we performed ChIP-Sequencing on chromatin-associated eNOS from cells from a primary tumor with poor outcome and from metastatic LNCaP cells. We found that: 1. the eNOS-bound regions (peaks) are widely distributed across the genome encompassing multiple transcription factors binding sites, including Estrogen Response Elements. 2. E2 increased the number of peaks, indicating hormone-dependent eNOS re-localization. 3. Peak distribution was similar with/without E2 with ? 55% of them in extragenic DNA regions and an intriguing involvement of the 5' domain of several miRs deregulated in PCa. Numerous potentially novel eNOS-targeted genes have been identified suggesting that eNOS participates in the regulation of large gene sets. The parallel finding of downregulation of a cluster of miRs, including miR-34a, in PCa cells associated with poor outcome led us to unveil a molecular link between eNOS and SIRT1, an epigenetic regulator of aging and tumorigenicity, negatively regulated by miR-34a and in turn activating eNOS. E2 potentiates miR-34a downregulation thus enhancing SIRT1 expression, depicting a novel eNOS/SIRT1 interplay fine-tuned by E2-activated ER signaling, and suggesting that eNOS may play an important role in aggressive PCa. (literal)
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