title: ERas protein is overexpressed and binds to the activated platelet-derived growth factor β receptor in bovine urothelial tumour cells associated with papillomavirus infection.
abstract: Embryonic stem cell-expressed Ras (ERas) encodes a constitutively active form of guanosine triphosphatase (GTPase) that binds to and activates phosphatidylinositol 3 kinase (PI3K), which in turn phosphorylates and activates downstream targets such as Akt. The current study evaluated ERas regulation and expression in papillomavirus-associated urothelial tumours in cattle grazing on lands rich in bracken fern. ERas was found upregulated and overexpressed by PCR, real time PCR and Western blot. Furthermore, protein overexpression was also confirmed by immunohistochemistry. ERas was found to interact physically and colocalise with the activated platelet derived growth factor β receptor (PDGFβR) by coimmunoprecipitation and laser scanning confocal investigations. Phosphorylation of Akt, a downstream effector both of ERas and PDGFβR, appeared to be increased in urothelial tumour cells. Altogether, these data indicate that ERas/PDGFβR complex could play a role in the pathogenesis of bovine papillomavirus-associated bladder neoplasia.
authors.affiliation: Dipartimento di Medicina Veterinaria e Produzioni Animali, Settore di Patologia Generale, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Russo
authors.affiliation: Dipartimento di Biologia, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Roperto
authors.affiliation: Dipartimento di Medicina Veterinaria e Produzioni Animali, Settore di Patologia Generale, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Iolanda
authors.initials: I
authors.lastname: Esposito
authors.affiliation: Dipartimento di Medicina Veterinaria e Produzioni Animali, Settore di Patologia Generale, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Dora Maria
authors.initials: DM
authors.lastname: Ceccarelli
authors.affiliation: Dipartimento di Medicina Veterinaria, Settore di Patologia ed Oncologia Comparata, Università di Bari, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zizzo
authors.affiliation: Dipartimento di Medicina Veterinaria, Università di Perugia, Perugia, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Leonardi
authors.affiliation: Dipartimento di Agraria, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Capparelli
authors.affiliation: Dipartimento di Medicina Veterinaria e Produzioni Animali, Settore di Patologia Generale, Università di Napoli Federico II, Napoli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borzacchiello
authors.affiliation: Dipartimento di Medicina Veterinaria e Produzioni Animali, Settore di Malattie Infettive, Università di Napoli Federico II, Napoli, Italy. Electronic address: sante.roperto@unina.it.
authors.forename: Sante
authors.initials: S
authors.lastname: Roperto
mesh_terms: D000818:Animals; D052688:Bovine papillomavirus 1 / Q000502:physiology; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D015689:Oncogene Protein p21(ras) / Q000235:genetics* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000235:genetics / Q000662:veterinary* / Q000821:virology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000662:veterinary* / Q000821:virology
chemical_list: D020797:Receptor, Platelet-Derived Growth Factor beta; D015689:Oncogene Protein p21(ras)
keywords: Cattle; Embryonic stem cell-expressed Ras (ERas); Papillomavirus E5 oncoprotein; Platelet-derived growth factor β receptor (PDGFβR); Urothelial tumours