α- sma - cre介导的PDK1切除揭示了PDK1在组织微环境中调控心肌细胞形态和肿瘤进展的重要作用

Pathologie-biologie Pub Date : 2015-04-01 DOI:10.1016/j.patbio.2014.12.004

X.-J. Qian , X.-L. Li , X. Xu , X. Wang , Q.-T. Feng , C.-J. Yang

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引用次数: 10

摘要

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)级联在心血管发展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。为了阐明PDK1对体内组织微环境的影响，我们建立了α- sma - cre介导的PDK1小鼠切除术。小鼠皮下注射Lewis肺癌细胞(LLC)。我们发现pdk1缺陷小鼠出现先天性扩张性心肌病，肿瘤生长减慢，肿瘤转移严重。组织病理分析显示心脏血管微环境异常及原发肿瘤。综上所述，PDK1通过干扰微环境在调节心功能和肿瘤转移中起关键作用。

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α-SMA-Cre-mediated excision of PDK1 reveals an essential role of PDK1 in regulating morphology of cardiomyocyte and tumor progression in tissue microenvironment

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.

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