Activated Platelet-Derived Growth Factor β Receptor Expression, PI3K-AKT Pathway Molecular Analysis, and Transforming Signals in Equine Sarcoids
Activated Platelet-Derived Growth Factor β Receptor Expression, PI3K-AKT Pathway Molecular Analysis, and Transforming Signals in Equine Sarcoids
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DOI：
10.1354/vp.08-vp-0191-b-fl
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发表时间：
2009-07-01
影响因子：
2.4
通讯作者：
Roperto, F.
中科院分区：
文献类型：
--
作者：
Borzacchiello, G.;Mogavero, S.;Roperto, F.
马肉瘤是马中最常见的皮肤肿瘤。牛乳头瘤病毒 (BPV) 1 型和 2 型与结节病有关，其中经常记录到主要转化癌蛋白 (E5) 的表达。病毒的转化活性是由于 E5 与血小板衍生生长因子 β 受体 (PDGF β-r) 的结合所致。在本研究中，我们通过 4 个肉瘤样本和 3 个正常马技能样本的蛋白质印迹显示，肉瘤组织中的 PDGF beta-r 比正常皮肤中的磷酸化程度更高 (P < .001)。此外，通过免疫共沉淀显示了激活的受体与磷脂酰肌醇-3-激酶 (PI3K) 的 85 kDa 调节亚基 (p85) 之间的物理相互作用。 PDGF beta-r 激活下游的 PI3K-AKT-细胞周期蛋白 D3 分子途径已被表达，并且所研究的分子数量高于正常值 (P < .001)，表明结节病中这些效应器被激活。此外，我们证明磷酸-JNK 和磷酸-JUN 在结节病中比在正常皮肤中表达更多。我们的结果为马结节病的发病机制提供了新的见解，并支持该体内模型的有效性，以进一步表征 BPV E5 诱导的致癌作用的分子途径。
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 beta receptor (PDGF beta-r). In the present study, we show by Western blot in 4 sarcoid samples and 3 normal equine skill samples that the PDGF beta-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 PDGF beta-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.