Department of Pharmacy, University of Salerno, Via Giovanni Paolo II n,132, 84084, Fisciano, Salerno, Italy.
Vet Res. 2013 Jul 22;44(1):61. doi: 10.1186/1297-9716-44-61.
In human cancer cells, BAG3 protein is known to sustain cell survival. Here, for the first time, we demonstrate the expression of BAG3 protein both in equine sarcoids in vivo and in EqS04b cells, a sarcoid-derived fully transformed cell line harbouring bovine papilloma virus (BPV)-1 genome. Evidence of a possible involvement of BAG3 in equine sarcoid carcinogenesis was obtained by immunohistochemistry analysis of tumour samples. We found that most tumour samples stained positive for BAG3, even though to a different grade, while normal dermal fibroblasts from healthy horses displayed very weak staining pattern for BAG3 expression. By siRNA technology, we demonstrate in EqS04b the role of BAG3 in counteracting basal as well as chemical-triggered pro-death signals. BAG3 down-modulation was indeed shown to promote cell death and cell cycle arrest in G0/G1. In addition, we found that BAG3 silencing sensitized EqS04b cells to phenethylisothiocyanate (PEITC), a promising cancer chemopreventive/chemotherapeutic agent present in edible cruciferous vegetables. Notably, such a pro-survival role of BAG3 was less marked in E. Derm cells, an equine BPV-negative fibroblast cell line taken as a normal counterpart. Altogether our findings might suggest a mutual cooperation between BAG3 and viral oncoproteins to sustain cell survival.
在人类癌细胞中，BAG3 蛋白被认为能维持细胞存活。在这里，我们首次证明了 BAG3 蛋白在体内马肉瘤和 EqS04b 细胞（一种携带牛乳头瘤病毒 (BPV)-1 基因组的完全转化的肉瘤衍生细胞系）中的表达。通过对肿瘤样本进行免疫组织化学分析，获得了 BAG3 可能参与马肉瘤发生的证据。我们发现，大多数肿瘤样本对 BAG3 呈阳性染色，尽管染色程度不同，但来自健康马的正常真皮成纤维细胞对 BAG3 表达的染色模式非常弱。通过 siRNA 技术，我们在 EqS04b 中证明了 BAG3 在对抗基础和化学触发的促死亡信号中的作用。BAG3 的下调确实促进了细胞死亡和细胞周期停滞在 G0/G1 期。此外，我们发现 BAG3 沉默使 EqS04b 细胞对苯乙基异硫氰酸盐（PEITC）敏感，PEITC 是一种存在于可食用十字花科蔬菜中的有前途的癌症化学预防/化疗药物。值得注意的是，在 E. Derm 细胞（作为正常对照的一种不含 BPV 的马成纤维细胞系）中，BAG3 的这种促生存作用不太明显。总之，我们的发现可能表明 BAG3 与病毒癌蛋白之间存在相互合作，以维持细胞存活。
