title: hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.
abstract: BACKGROUND
  hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking.
  
  
  METHODS
  hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb.
  
  
  RESULTS
  (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo.
  
  
  CONCLUSIONS
  hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Lastraioli
authors.affiliation: Department of Pathology, Pathology Unit, Campus Bio-Medico University, via del Portillo 200, Rome 00128, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Perrone
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sette
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Fiore
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Crociani
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Manoli
authors.affiliation: 1] Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy [2] DI.V.A.L Toscana Srl, Via Madonna del Piano 6, Sesto Fiorentino 50019, Italy.
authors.forename: M
authors.initials: M
authors.lastname: D'Amico
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Masselli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Iorio
authors.affiliation: Department of Pathology, Pathology Unit, Campus Bio-Medico University, via del Portillo 200, Rome 00128, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Callea
authors.affiliation: Department of General Surgery, Campus Bio-Medico University, via del Portillo 200, Rome 00128, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Borzomati
authors.affiliation: Department of General Surgery, Campus Bio-Medico University, via del Portillo 200, Rome 00128, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Nappo
authors.affiliation: Casa di Cura Villa Margherita, Viale di Villa Massimo 48, Rome 00161, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bartolozzi
authors.affiliation: Department of Medical Oncology, Campus Bio-Medico University, via del Portillo 200, Rome 00128, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Santini
authors.affiliation: Department of General Surgery and Surgical Oncology, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, Florence 50134, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bencini
authors.affiliation: Department of General Surgery and Surgical Oncology, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, Florence 50134, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Farsi
authors.affiliation: Clinical Trials Coordinating Center, Azienda Ospedaliero-Universitaria Careggi/Istituto Toscano Tumori, Largo Brambilla 3, Florence 50134, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Boni
authors.affiliation: Department of Medical Oncology, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, Florence 50134, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Di Costanzo
authors.affiliation: Physiologisches Institut II, University of Münster, Robert-Koch-Str. 27b, Münster D-48149, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schwab
authors.affiliation: Department of Pathology, Pathology Unit, Campus Bio-Medico University, via del Portillo 200, Rome 00128, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Onetti Muda
authors.affiliation: Department of General Surgery, Campus Bio-Medico University, via del Portillo 200, Rome 00128, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Coppola
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, Florence 50134, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Arcangeli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D000072237:ERG1 Potassium Channel; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D066246:ErbB Receptors