Activated platelet-derived growth factor beta receptor expression, PI3K-AKT pathway molecular analysis, and transforming signals in equine sarcoids.
Authors: Borzacchiello G, Mogavero S, De Vita G, Roperto S, Della Salda L, Roperto F
Journal: Veterinary pathology
Summary
# Editorial Summary: Molecular Pathways in Equine Sarcoid Development Equine sarcoids represent the most prevalent skin tumour in horses, with bovine papillomavirus (BPV) types 1 and 2 playing a central aetiological role through expression of the E5 oncoprotein. Borzacchiello and colleagues used Western blotting and coimmunoprecipitation techniques to investigate receptor signalling in sarcoid tissue versus normal equine skin, examining the activation status of the platelet-derived growth factor beta receptor (PDGFβ-R) and downstream effector molecules. The research demonstrated significantly elevated phosphorylation of PDGFβ-R in sarcoid samples compared with controls (P < 0.001), with physical interaction confirmed between the activated receptor and the PI3K regulatory subunit (p85), indicating genuine signal transduction through the PI3K-AKT-cyclin D3 pathway—all molecules present at substantially higher concentrations in neoplastic tissue (P < 0.001). The authors additionally identified upregulation of phosphorylated JNK and JUN proteins in sarcoid lesions, suggesting activation of multiple proliferative signalling cascades. These molecular findings provide mechanistic insight into BPV E5-mediated transformation and may inform future therapeutic strategies targeting these activated pathways, particularly for cases where conventional treatments prove ineffective or where understanding tumour biology could guide targeted interventions.
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Practical Takeaways
- •Understanding BPV E5-induced molecular pathways in sarcoids may inform development of targeted therapeutic interventions beyond current surgical and immunological approaches
- •PDGFbeta-r activation represents a potential diagnostic marker or therapeutic target for equine sarcoid management
- •This molecular characterization establishes equine sarcoid as a valuable in-vivo model for studying BPV-induced carcinogenesis mechanisms
Key Findings
- •PDGFbeta-r is significantly more phosphorylated in sarcoid tissue compared to normal equine skin (P < 0.001)
- •PI3K-AKT-cyclin D3 molecular pathway is activated downstream of PDGFbeta-r in sarcoids with higher expression than normal tissue (P < 0.001)
- •Physical interaction between activated PDGFbeta-r and PI3K p85 regulatory subunit demonstrated via coimmunoprecipitation in sarcoid samples
- •Phospho-JNK and phospho-JUN are more highly expressed in sarcoid tissue than in normal skin