Intracellular estrogen receptor-binding fragment-associated antigen 9 exerts in vivo tumor-promoting effects via its coiled-coil region
Intracellular estrogen receptor-binding fragment-associated antigen 9 exerts in vivo tumor-promoting effects via its coiled-coil region
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DOI：
10.3892/ijo.2011.1026
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发表时间：
2011-07-01
影响因子：
5.2
通讯作者：
Ariga, Tadashi
中科院分区：
文献类型：
--
作者：
Maeyama, Yoshihiro;Otsu, Makoto;Ariga, Tadashi
雌激素受体结合片段相关抗原9（EBAG 9）是一种功能尚不清楚的肿瘤促进因子。为了评估EBAG 9在晚期恶性肿瘤中的致病作用，我们使用逆转录病毒介导的基因转导产生了稳定表达全长或截短EBAG 9蛋白的EG 7-OVA和MethA小鼠肿瘤细胞系。在皮下接种到免疫活性小鼠后，当全长EBAG 9过表达时，两种细胞系均显示出体内肿瘤生长的显著加速。有趣的是，删除卷曲螺旋区域，从而产生截短的EBAG 9蛋白，消除了肿瘤加速效应，确立了该结构域在EBAG 9介导的肿瘤促进中的重要性。然而，在表达全长或截短的EBAG 9蛋白的这些肿瘤细胞系中，体外细胞增殖或MHC I类和共刺激分子的表达水平没有改变，这些分子被认为在肿瘤细胞的免疫逃避中起作用。此外，全长和截短的EBAG 9蛋白在肿瘤细胞中均显示出主要的细胞质定位。总的来说，这些结果表明EBAG 9过表达可能是增强肿瘤细胞恶性性质的原因，并且肿瘤促进可能需要EBAG 9通过卷曲螺旋区与尚未鉴定的结合配偶体细胞内缔合。
Estrogen receptor-binding fragment-associated antigen 9 (EBAG9) is a tumor-promoting factor of largely unknown function. To assess a causative role of EBAG9 in advanced malignancies, we generated the EG7-OVA and MethA murine tumor cell lines that stably express full-length or truncated EBAG9 protein, using retroviral-mediated gene transduction. Upon subcutaneous inoculation into immunocompetent mice, both cell lines showed marked acceleration of in vivo tumor growth when full-length EBAG9 was overexpressed. Interestingly, deletion of the coiled-coil region, thereby producing truncated EBAG9 protein, abolished the tumor-acceleration effect, establishing the importance of this domain in EBAG9-mediated tumor promotion. However, there was no alteration in in vitro cell proliferation or expression levels of MHC class I and co-stimulatory molecules believed to play a role in immune evasion of tumor cells in these tumor cell lines expressing full-length or truncated EBAG9 protein. Furthermore, both full-length and truncated EBAG9 proteins showed a predominantly cytoplasmic localization in the tumor cells. Collectively, these results suggest that EBAG9 overexpression can be causative in enhancing the malignant properties of tumor cells, and that tumor promotion likely requires EBAG9 intracellular association with as yet unidentified binding partners via the coiled-coil region.