A large animal model to evaluate the effects of Hsp90 inhibitors for the treatment of lung adenocarcinoma.
A large animal model to evaluate the effects of Hsp90 inhibitors for the treatment of lung adenocarcinoma.
复制标题
评估Hsp90抑制剂治疗肺腺癌效果的大型动物模型。
DOI：
10.1016/j.virol.2007.09.041
复制
发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Palmarini,Massimo
中科院分区：
文献类型：
--
作者：
Varela,Mariana;Golder,Matthew;Archer,Fabienne;delasHeras,Marcelo;Leroux,Caroline;Palmarini,Massimo
绵羊肺腺癌(OPA)是由Jaagsiekte绵羊逆转录病毒(JSRV)引起的绵羊自然发生的肺癌。JSRV包膜糖蛋白(Env)在体外和体内都是主要的癌蛋白。为了开发OPA作为肺癌模型的基础，我们筛选了多种信号转导抑制剂来阻断JSRV Env的转化。大多数抑制剂不能有效地阻断JSRV env诱导的转化。相反，各种Hsp90抑制剂能有效地阻断JSRV的转化。这种现象至少部分是由于Akt的降解，Akt在JSRV转化的细胞中被激活。在自然发生OPA的绵羊肿瘤细胞中发现了HSP90的表达。此外，Hsp90抑制剂特异性地抑制来自OPA肿瘤的永生化细胞以及原代细胞的增殖。因此，OPA可作为全面研究Hsp90抑制剂在肺腺癌中作用的大型动物模型。
Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring lung cancer of sheep caused by Jaagsiekte sheep retrovirus (JSRV). The JSRV envelope glycoprotein (Env) functions as a dominant oncoprotein in vitro and in vivo. In order to develop the basis for the use of OPA as a lung cancer model, we screened a variety of signal transduction inhibitors for their ability to block transformation by the JSRV Env. Most inhibitors were not effective in blocking JSRV Env-induced transformation. On the contrary, various Hsp90 inhibitors efficiently blocked JSRV transformation. This phenomenon was at least partly due to Akt degradation, which is activated in JSRV-transformed cells. Hsp90 was found expressed in tumor cells of sheep with naturally occurring OPA. In addition, Hsp90 inhibitors specifically inhibited proliferation of immortalized and moreover primary cells derived from OPA tumors. Thus, OPA could be used as a large animal model for comprehensive studies investigating the effects of Hsp90 inhibitors in lung adenocarcinoma.