Regulator of G-Protein Signaling 5 Reduces HeyA8 Ovarian Cancer Cell Proliferation and Extends Survival in a Murine Tumor Model.
Regulator of G-Protein Signaling 5 Reduces HeyA8 Ovarian Cancer Cell Proliferation and Extends Survival in a Murine Tumor Model.
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DOI：
10.1155/2012/518437
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发表时间：
2012
影响因子：
3
通讯作者：
Murph MM
中科院分区：
文献类型：
--
作者：
Altman MK;Nguyen DT;Patel SB;Fambrough JM;Beedle AM;Hardman WJ;Murph MM
g蛋白信号传导5的调节因子（RGS5）属于GTPase激活因子家族，它终止由细胞外介质和g蛋白偶联受体启动的信号级联反应。RGS5具有有趣的双重生物学作用。RGS5的一个功能作用是作为周细胞生物标志物，影响恶性进展过程中血管生成的转换。它的另一个功能是促进缺氧环境下的细胞凋亡。我们着手阐明RGS5表达在多大程度上调控肿瘤进展——它在卵巢肿瘤生物学中是起致病作用还是起保护作用。因此，我们构建了一个诱导基因表达系统，实现了RGS5在HeyA8-MDR卵巢癌细胞中的表达。通过这项研究，我们观察到，可诱导的RGS5表达显著减少体外brdu阳性HeyA8-MDR细胞，尽管这与体内卵巢癌小鼠模型中观察到的肿瘤体积减少无关。有趣的是，与对照组相比，携带rgs5表达肿瘤的小鼠的存活率增加，这可能是由于病理检查中观察到的大面积坏死。此外，携带rgs5表达肿瘤的小鼠发生肿瘤溃疡的可能性较小。综上所述，这些数据支持了RGS5的时间表达和稳定可能是调节肿瘤进展的多组分方法中有价值的策略。
The regulator of G-protein signaling 5 (RGS5) belongs to a family of GTPase activators that terminate signaling cascades initiated by extracellular mediators and G-protein-coupled receptors. RGS5 has an interesting dual biological role. One functional RGS5 role is as a pericyte biomarker influencing the switch to angiogenesis during malignant progression. Its other functional role is to promote apoptosis in hypoxic environments. We set out to clarify the extent to which RGS5 expression regulates tumor progression—whether it plays a pathogenic or protective role in ovarian tumor biology. We thus constructed an inducible gene expression system to achieve RGS5 expression in HeyA8-MDR ovarian cancer cells. Through this we observed that inducible RGS5 expression significantly reduces in vitro BrdU-positive HeyA8-MDR cells, although this did not correlate with a reduction in tumor volume observed using an in vivo mouse model of ovarian cancer. Interestingly, mice bearing RGS5-expressing tumors demonstrated an increase in survival compared with controls, which might be attributed to the vast regions of necrosis observed by pathological examination. Additionally, mice bearing RGS5-expressing tumors were less likely to have ulcerated tumors. Taken together, this data supports the idea that temporal expression and stabilization of RGS5 could be a valuable tactic within the context of a multicomponent approach for modulating tumor progression.