BTG2 loss and miR-21 upregulation contribute to prostate cell transformation by inducing luminal markers expression and epithelial-mesenchymal transition

Ruggero De Maria Marchiano, Valeria Coppola, Federica Francescangeli, Alfredo Pagliuca, V. Coppola, M. Musumeci, M. Patrizii, A. Cannistraci, A. Addario, M. Maugeri-Saccà, M. Biffoni, F. Francescangeli, M. Cordenonsi, S. Piccolo, L. Memeo, A. Pagliuca, G. Muto, A. Zeuner, D. Bonci

Risultato della ricerca: Contributo in rivistaArticolo in rivista

71 Citazioni (Scopus)

Abstract

Prostate cancer is one of the leading causes of cancer-related death in men. Despite significant advances in prostate cancer diagnosis and management, the molecular events involved in the transformation of normal prostate cells into cancer cells have not been fully understood. It is generally accepted that prostate cancer derives from the basal compartment while expressing luminal markers. We investigated whether downregulation of the basal protein B-cell translocation gene 2 (BTG2) is implicated in prostate cancer transformation and progression. Here we show that BTG2 loss can shift normal prostate basal cells towards luminal markers expression, a phenotype also accompanied by the appearance of epithelial-mesenchymal transition (EMT) traits. We also show that the overexpression of microRNA (miR)-21 suppresses BTG2 levels and promotes the acquisition of luminal markers and EMT in prostate cells. Furthermore, by using an innovative lentiviral vector able to compete with endogenous mRNA through the overexpression of the 3′-untranslated region of BTG2, we demonstrate that in prostate tumor cells, the levels of luminal and EMT markers can be reduced by derepression of BTG2 from microRNA-mediated control. Finally, we show that the loss of BTG2 expression confers to non-tumorigenic prostate cells ability to grow in an orthotopic murine model, thus demonstrating the central role of BTG2 downregulaton in prostate cancer biology. © 2013 Macmillan Publishers Limited. All rights reserved.
Lingua originaleEnglish
pagine (da-a)1843-1853
Numero di pagine11
RivistaOncogene
Volume32
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • Animals
  • Apoptosis
  • BTG2
  • Biomarkers, Tumor
  • Blotting, Western
  • Cancer Research
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Cells, Cultured
  • EMT
  • Epithelial-Mesenchymal Transition
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genetics
  • Humans
  • Immediate-Early Proteins
  • Male
  • Mice
  • MicroRNAs
  • Molecular Biology
  • Prostate
  • Prostatic Neoplasms
  • RNA, Messenger
  • RNA, Small Interfering
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Proteins
  • basal and luminal phenotype
  • microRNA
  • prostate cancer

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