title: Expression of platelet derived growth factor β receptor, its activation and downstream signals in bovine cutaneous fibropapillomas.
abstract: Bovine cutaneous fibropapillomas are benign skin tumours formed by proliferation of epidermal keratinocytes and dermal fibroblasts caused by bovine papillomaviruses (BPVs). BPV E5 oncoprotein plays a key role in neoplastic cell transformation by specifically binding to the platelet derived growth factor beta receptor (PDGFβR) causing its phosphorylation and activation of proliferation and survival signal transduction pathways, among these phosphatidyl inositol-3-kinase (PI3K)/Akt and Ras-mitogen-activated-protein-kinase-Erk (Ras-MAPK-Erk) pathways. The aim of this study was to investigate the expression of PDGFβR, its phosphorylation status and expression of the downstream molecules phospho-Akt (pAkt) and phospho-Erk (pErk), in naturally occurring bovine cutaneous fibropapillomas. By immunohistochemistry on serial sections we showed cytoplasmic co-expression of the PDGFβR and E5 protein in neoplastic tissue. Western blot analysis revealed that PDGFβR was phosphorylated in higher amount in tumour samples compared to normal skin. pAkt, but not pErk, was also overexpressed in tumour samples. These findings may provide new insights into the aetiopathogenic mechanisms underlying naturally occurring bovine fibropapillomas and contribute to understanding the molecular scenario underlying BPV induced tumourigenesis.
authors.affiliation: Department of Public Health, Faculty of Veterinary Medicine, University of Agriculture Sciences and Veterinary Medicine Ion Ionescu de la Brad, Iasi, Romania.
authors.forename: F
authors.initials: F
authors.lastname: Bocaneti
authors.forename: G
authors.initials: G
authors.lastname: Altamura
authors.forename: A
authors.initials: A
authors.lastname: Corteggio
authors.forename: M
authors.initials: M
authors.lastname: Martano
authors.forename: F
authors.initials: F
authors.lastname: Roperto
authors.forename: E
authors.initials: E
authors.lastname: Velescu
authors.forename: G
authors.initials: G
authors.lastname: Borzacchiello
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D052688:Bovine papillomavirus 1 / Q000378:metabolism*; D002417:Cattle; D002418:Cattle Diseases / Q000378:metabolism / Q000821:virology*; D004591:Electrophoresis, Polyacrylamide Gel / Q000662:veterinary; D020935:MAP Kinase Signaling System / Q000502:physiology; D051058:Oncogene Protein v-akt / Q000378:metabolism / Q000502:physiology; D009856:Oncogene Proteins, Viral / Q000378:metabolism / Q000502:physiology; D030361:Papillomavirus Infections / Q000378:metabolism / Q000662:veterinary*; D010766:Phosphorylation; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D009856:Oncogene Proteins, Viral; C054304:oncogene protein E5, Bovine papillomavirus type 1; D020797:Receptor, Platelet-Derived Growth Factor beta; D051058:Oncogene Protein v-akt