title: A large animal model to evaluate the effects of Hsp90 inhibitors for the treatment of lung adenocarcinoma.
abstract: Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The JSRV envelope glycoprotein (Env) functions as a dominant oncoprotein in vitro and in vivo. In order to develop the basis for the use of OPA as a lung cancer model, we screened a variety of signal transduction inhibitors for their ability to block transformation by the JSRV Env. Most inhibitors were not effective in blocking JSRV Env-induced transformation. On the contrary, various Hsp90 inhibitors efficiently blocked JSRV transformation. This phenomenon was at least partly due to Akt degradation, which is activated in JSRV-transformed cells. Hsp90 was found expressed in tumor cells of sheep with naturally occurring OPA. In addition, Hsp90 inhibitors specifically inhibited proliferation of immortalized and moreover primary cells derived from OPA tumors. Thus, OPA could be used as a large animal model for comprehensive studies investigating the effects of Hsp90 inhibitors in lung adenocarcinoma.
authors.affiliation: Institute of Comparative Medicine, University of Glasgow Veterinary School, 464 Bearsden Road, Glasgow, G61 1QH, Scotland, UK.
authors.forename: Mariana
authors.initials: M
authors.lastname: Varela
authors.forename: Matthew
authors.initials: M
authors.lastname: Golder
authors.forename: Fabienne
authors.initials: F
authors.lastname: Archer
authors.forename: Marcelo
authors.initials: M
authors.lastname: de las Heras
authors.forename: Caroline
authors.initials: C
authors.lastname: Leroux
authors.forename: Massimo
authors.initials: M
authors.lastname: Palmarini
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D000818:Animals; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000627:therapeutic use*; D007150:Immunohistochemistry; D022141:Jaagsiekte sheep retrovirus; D008175:Lung Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology; D034561:Sheep, Domestic
chemical_list: D018841:HSP90 Heat-Shock Proteins