α-SMA-Cre介导的PDK1基因敲除揭示了PDK1在调节心肌细胞形态和组织微环境中肿瘤进展方面的重要作用。
α-SMA-Cre-mediated excision of PDK1 reveals an essential role of PDK1 in regulating morphology of cardiomyocyte and tumor progression in tissue microenvironment.
作者信息
Qian X-J, Li X-L, Xu X, Wang X, Feng Q-T, Yang C-J
机构信息
Department of Cardiology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China; Department of Pneumology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China.
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
出版信息
Pathol Biol (Paris). 2015 Apr;63(2):91-100. doi: 10.1016/j.patbio.2014.12.004. Epub 2015 Jan 16.
The phosphoinositide-3 kinase (PI3K) - phosphoinositide-dependent protein kinase 1 (PDK1)-Akt/protein kinase B (PKB) cascade plays a critical role in cardiovascular development and tumor genesis. But the role of PDK1 in the microenvironment of heart and tumor remains unknown. To clarify the effects of PDK1 on tissue microenvironment in vivo, here, we created α-SMA-Cre-mediated excision of PDK1 mice. And the mice were injected subcutaneously with Lewis lung carcinoma (LLC) cells. We found PDK1-deficient mice had post-natal praecox dilated cardiomyopathy, decelerated tumor growth and severe tumor metastasis. Histopathological analysis revealed abnormality of vascular microenvironment in heart and primary tumor. In conclusion, PDK1 plays a pivotal role in regulating cardiac function and tumor metastasis by interfering with microenvironment.
磷酸肌醇-3激酶（PI3K）-磷酸肌醇依赖性蛋白激酶1（PDK1）-Akt/蛋白激酶B（PKB）级联反应在心血管发育和肿瘤发生中起关键作用。但PDK1在心脏和肿瘤微环境中的作用尚不清楚。为阐明PDK1在体内对组织微环境的影响，在此我们构建了α-SMA-Cre介导的PDK1基因敲除小鼠。然后将小鼠皮下注射Lewis肺癌（LLC）细胞。我们发现PDK1缺陷小鼠出生后出现早发性扩张型心肌病，肿瘤生长减缓且严重转移。组织病理学分析显示心脏和原发性肿瘤的血管微环境异常。总之，PDK1通过干扰微环境在调节心脏功能和肿瘤转移中起关键作用。
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