Abstract:
Ovine pulmonary adenocarcinoma (OPA), caused by the jaagsiekte sheep retrovirus (JSRV), is a chronic, progressive, and contagious lung tumor that seriously affects sheep production. It also represents a valuable animal model for several human lung adenocarcinomas. However, little is known about the role of autophagy in OPA tumorigenesis. Here, Western blotting combined with transmission electron microscopy examination and Cyto-ID dye staining was employed for evaluation of changes of autophagic levels. The results of the present study showed that expression of the autophagy marker proteins Beclin-1 and LC3 was decreased in OPA lung tissues, as well as in cells overexpressing the envelope glycoprotein of JSRV (JSRV Env). Reduced numbers of autophagosomes were also observed in cells overexpressing JSRV Env, although assessment of autophagic flux showed that JSRV Env overexpression did not block the formation of autophagosomes, suggesting increased degradation of autolysosomes. Last, mouse xenograft experiments indicated that inhibition of autophagy by 3-methyladenine suppressed both tumor growth and the epithelial-to-mesenchymal transition. In conclusion, JSRV, through JSRV Env, takes advantage of the autophagy process, leading to the development of OPA.
摘要:
绵羊肺腺癌(OPA),由jaagsiekte绵羊逆转录病毒(JSRV)引起,是慢性的,进步,严重影响绵羊生产的传染性肺部肿瘤。它还代表了几种人肺腺癌的有价值的动物模型。然而,关于自噬在OPA肿瘤发生中的作用知之甚少。这里,免疫印迹结合透射电镜检查和Cyto-ID染料染色评价自噬水平的变化。本研究的结果表明,自噬标记蛋白Beclin-1和LC3在OPA肺组织中的表达降低,以及过表达JSRV包膜糖蛋白(JSRVEnv)的细胞。在过表达JSRVEnv的细胞中也观察到自噬体数量减少,尽管对自噬通量的评估表明JSRVEnv过表达并不阻断自噬体的形成,表明自体溶酶体的降解增加。最后,小鼠异种移植实验表明,3-甲基腺嘌呤对自噬的抑制作用抑制了肿瘤的生长和上皮-间质转化。总之,JSRV,通过JSRVEnv,利用自噬过程,导致OPA的发展。