Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation
Effect of cigarette smoke exposure and mutant Kras overexpression on pancreatic cell proliferation
复制标题
DOI：
10.3892/ol.2017.5606
复制
发表时间：
2017-03-01
期刊：
影响因子：
2.9
通讯作者：
Gairola, C. Gary
中科院分区：
文献类型：
--
作者：
Glauert, Howard P.;Elliott, R. Scott;Gairola, C. Gary
胰腺癌是癌症相关死亡的第四大原因。胰腺癌的主要危险因素是吸烟。Kras突变在人类胰腺癌中很常见。本研究检验了一种假设，即暴露于香烟烟雾和胰腺中Kras突变基因的过度表达会影响小鼠胰腺细胞的增殖。在胰腺中过表达Kras突变基因（Kras (G12D)）的小鼠以及野生型小鼠暴露于环境烟草烟雾中2周。Kras突变体的过表达增加了胰腺导管细胞、腺泡细胞和胰岛细胞的细胞增殖。值得注意的是，香烟烟雾暴露降低了胰腺导管细胞和腺泡细胞的细胞增殖，而对胰岛细胞没有影响。吸烟不会影响胰腺中肿瘤坏死因子(TNF) α、p53或细胞周期蛋白D1的蛋白水平，但突变体Kras过表达会略微降低TNF α和p53蛋白水平。因此，在过表达Kras突变体的小鼠中，胰腺细胞增殖与胰腺肿瘤的后期发展有关，但香烟烟雾对胰腺细胞增殖的影响并不能为人类胰腺癌的发生提供良好的模型。
Pancreatic cancer is the fourth leading cause of cancer-associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRas(G12D)) in the pancreas as well as wild-type mice were exposed to environmental tobacco smoke for 2 weeks. Overexpression of mutant Kras increased cell proliferation in pancreatic ductal, acinar and islet cells. Notably, cigarette smoke exposure decreased cell proliferation in pancreatic ductal and acinar cells, and had no effect in islet cells. Cigarette smoke did not affect pancreatic protein levels of tumor necrosis factor (TNF)alpha, p53, or cyclin D1, but mutant Kras overexpression slightly decreased TNF alpha and p53 protein levels. Therefore, pancreatic cell proliferation in mice overexpressing mutant Kras is associated with the later development of pancreatic tumors, but effects of cigarette smoke on pancreatic cell proliferation do not provide a good model for human pancreatic carcinogenesis.