Activated Platelet-Derived Growth Factor β Receptor Expression, P13K-AKT Pathway Molecular Analysis, and Transforming Signals in Equine Sarcoids

Abstract

The equine sarcoid is the most common dermatologic neoplasm reported in horses. Bovine papillomavirus (BPV) types 1 and 2 are associated with sarcoids, in which the expression of the major transforming oncoprotein (E5) is often recorded. The transformation activity of the virus is due to the binding of the E5 to the platelet-derived growth factor β receptor (PDGFβ-r). In the present study, we show by Western blot in 4 sarcoid samples and 3 normal equine skin samples that the PDGFβ-r is more phosphorylated in sarcoid tissue than in normal skin ( P < .001). Furthermore, the physical interaction between the activated receptor and the 85-kDa regulatory subunit (p85) of phosphatidylinositol-3-kinase (PI3K) is shown by coimmunoprecipitation. The PI3K-AKT-cyclin D3 molecular pathway downstream to the activation of the PDGFβ-r is shown to be expressed, and the amount of the investigated molecules is higher than normal ( P < .001), suggesting an activation of these effectors in sarcoids. Further, we demonstrate that phospho-JNK and phospho-JUN are more expressed in sarcoids than in normal skin. Our results provide new insights into the pathogenesis of equine sarcoids and support the validity of this in-vivo model to further characterize the molecular pathways underlying BPV E5-induced carcinogenesis.