title: Receptor-Independent Ectopic Activity of Prolactin Predicts Aggressive Lung Tumors and Indicates HDACi-Based Therapeutic Strategies.
abstract: OBJECTIVE
  Ectopic activation of tissue-specific genes accompanies malignant transformation in many cancers. Prolactin (PRL) aberrant activation in lung cancer was investigated here to highlight its value as a biomarker.
  
  
  RESULTS
  PRL is ectopically activated in a subset of very aggressive lung tumors, associated with a rapid fatal outcome, in our cohort of 293 lung tumor patients and in an external independent series of patients. Surprisingly PRL receptor expression was not detected in the vast majority of PRL-expressing lung tumors. Additionally, the analysis of the PRL transcripts in lung tumors and cell lines revealed systematic truncations of their 5' regions, including the signal peptide-encoding portions. PRL expression was found to sustain cancer-specific gene expression circuits encompassing genes that are normally responsive to hypoxia. Interestingly, this analysis also indicated that histone deacetylase (HDAC) inhibitors could counteract the PRL-associated transcriptional activity.
  
  
  CONCLUSIONS
  Altogether, this work not only unravels a yet unknown oncogenic mechanism but also indicates that the specific category of PRL-expressing aggressive lung cancers could be particularly responsive to an HDAC inhibitor-based treatment.
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Aurore
authors: A
authors: Le Bescont
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Anne-Laure
authors: AL
authors: Vitte
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Alexandra
authors: A
authors: Debernardi
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Sandrine
authors: S
authors: Curtet
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Thierry
authors: T
authors: Buchou
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Jessica
authors: J
authors: Vayr
authors: 2 Cartes d'Identité des Tumeurs Program, Ligue Nationale Contre le Cancer , Paris, France .
authors: Aurélien
authors: A
authors: de Reyniès
authors: 3 Chemical Genetics Laboratory , RIKEN, Wako, Japan .
authors: Akihiro
authors: A
authors: Ito
authors: 4 INSERM U892, Centre de Recherche sur le Cancer Nantes Angers and UMR_S 892, Université d'Angers , Plateforme SNP, Transcriptome & Epigénomique, Centre Hospitalier Universitaire d'Angers, Angers, France .
authors: Philippe
authors: P
authors: Guardiola
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Christian
authors: C
authors: Brambilla
authors: 3 Chemical Genetics Laboratory , RIKEN, Wako, Japan .
authors: Minoru
authors: M
authors: Yoshida
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Elisabeth
authors: E
authors: Brambilla
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Sophie
authors: S
authors: Rousseaux
authors: 1 INSERM U823, Université Joseph Fourier-Grenoble 1 , Institut Albert Bonniot, Grenoble, France .
authors: Saadi
authors: S
authors: Khochbin
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011379:Prognosis; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011981:Receptors, Prolactin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D056572:Histone Deacetylase Inhibitors; D012333:RNA, Messenger; D011981:Receptors, Prolactin; D011388:Prolactin