Sakai Toshitaka, Mashima Hirosato, Yamada Yumi, Goto Takashi, Sato Wataru, Dohmen Takahiro, Kamada Kentaro, Yoshioka Masato, Uchinami Hiroshi, Yamamoto Yuzo, Ohnishi Hirohide
From the Departments of *Gastroenterology and †Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita, Japan.
Pancreas. 2014 Aug;43(6):909-16. doi: 10.1097/MPA.0000000000000116.
Pancreatic cancer is one of the most malignant diseases worldwide. Interferon regulatory factor (IRF) 1 and IRF2 function as a tumor suppressor and oncoprotein, respectively, in several types of cancers. We investigated whether IRF1 and IRF2 are involved in the progression of pancreatic cancer.
We examined the expressions of IRF1 and IRF2 in pancreatic cancer specimens and analyzed the association with clinicopathologic features. We evaluated the biological effects of IRF1 and IRF2 using a pancreatic cancer cell line.
The expression levels of IRF1 and IRF2 were decreased and increased, respectively, in the pancreatic cancer cells compared with those observed in the paired normal areas. A higher expression of IRF1 was associated with better features of tumor differentiation, infiltration depth, tumor size, and survival, whereas that of IRF2 was associated with a worse feature of tumor infiltration depth. Interferon regulatory factor 2-overexpressing PANC-1 cells exhibited an increase in cell growth, less apoptotic features, and chemoresistance to gemcitabine treatment. In contrast, IRF1-overexpressing cells exhibited the opposite characteristics.
Interferon regulatory factors 1 and 2 may regulate the progression of pancreatic cancer by functioning as an antioncoprotein and oncoprotein, respectively. These molecules may serve as potential targets of therapy.
胰腺癌是全球最恶性的疾病之一。在几种癌症中，干扰素调节因子（IRF）1和IRF2分别发挥肿瘤抑制因子和癌蛋白的作用。我们研究了IRF1和IRF2是否参与胰腺癌的进展。
我们检测了胰腺癌标本中IRF1和IRF2的表达，并分析其与临床病理特征的相关性。我们使用胰腺癌细胞系评估IRF1和IRF2的生物学效应。
与配对的正常组织相比，胰腺癌细胞中IRF1的表达水平降低，而IRF2的表达水平升高。IRF1的高表达与肿瘤分化、浸润深度、肿瘤大小和生存的较好特征相关，而IRF2的高表达与肿瘤浸润深度的较差特征相关。过表达IRF2的PANC-1细胞表现出细胞生长增加、凋亡特征减少以及对吉西他滨治疗的化疗耐药性。相反，过表达IRF1的细胞表现出相反的特征。
干扰素调节因子1和2可能分别作为抗癌蛋白和癌蛋白调节胰腺癌的进展。这些分子可能成为潜在的治疗靶点。
