Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer
Fra-1 is upregulated in gastric cancer tissues and affects the PI3K/Akt and p53 signaling pathway in gastric cancer
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Fra-1在胃癌组织中表达上调并影响胃癌中PI3K/Akt和p53信号通路
DOI：
10.3892/ijo.2015.3146
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发表时间：
2015-11-01
影响因子：
5.2
通讯作者：
Zhou, Yanhong
中科院分区：
文献类型：
--
作者：
He, Junyu;Zhu, Guangchao;Zhou, Yanhong
胃癌是一种侵袭性疾病，继续对全球健康产生令人生畏的影响。Fra-1（FOSL 1）在多种恶性肿瘤的发生中起重要作用。我们通过qPCR、免疫组化（IHC）和western blot技术研究了胃癌（GC）组织中Fra-1的表达。结果显示，Fra-1在胃癌组织中的表达高于癌旁组织。为探讨Fra-1在胃癌中的作用机制，我们研究了Fra-1对胃癌细胞AGS凋亡和细胞周期的影响，发现Fra-1过表达的AGS细胞凋亡明显减少，S期细胞比例增加。我们通过LC-MS/MS分析和western blot技术鉴定并证实Fra-1在体外影响CTTN和EZR的表达水平。此外，我们发现Fra-1与胃癌组织中PI 3 K/Akt和p53信号通路的失调有关。此外，我们发现Fra-1过表达影响体内PI 3 K，Akt，MDM 2和p53的表达。综上所述，我们的研究结果表明，Fra-1在胃癌组织中上调，并通过影响PI 3 K/Akt和p53信号通路发挥其功能。
Gastric cancer is an aggressive disease that continues to have a daunting impact on global health. Fra-1 (FOSL1) plays important roles in oncogenesis in various malignancies. We investigated the expression of Fra-1 in gastric cancer (GC) tissues by qPCR, immunohistochemistry (IHC) and western blot technologies. The results showed that Fra-1 was overexpressed in gastric cancer tissues compared with the adjacent non-cancerous tissues. To explore the possible mechanism of Fra-1 in GC, we elucidated the effect of Fra-1 in the apoptosis and cell cycle of gastric cancer cells, AGS, and found that a considerable decrease in apoptotic cells and increase of S phase rate were observed for AGS cells with Fra-1 overexpession. We identified and confirmed that Fra-1 affected the expression level of CTTN and EZR in vitro through LC-MS/MS analyses and western blot technology. Furthermore, we found that Fra-1 was correlated with dysregulation PI3K/Akt and p53 signaling pathway in gastric cancer tissues in vitro. Moreover, we found that Fra-1 overexpression affected the expression of PI3K, Akt, MDM2 and p53 in vivo. In summary, our results suggest that Fra-1 is upregulated in gastric cancer tissues and plays its function by affecting the PI3K/Akt and p53 signaling pathway in gastric cancer.