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IQGAPs和Ras家族在肝细胞癌实验小鼠模型中的基因表达:癌症进展的机制研究

Gene expression of IQGAPs and Ras families in an experimental mouse model for hepatocellular carcinoma: a mechanistic study of cancer progression.

作者信息

Zoheir Khairy M A, Abd-Rabou Ahmed A, Harisa Gamaleldin I, Ashour Abdelkader E, Ahmad Sheikh Fayaz, Attia Sabry M, Bakheet Saleh A, Abdel-Hamied Hala E, Abd-Allah Adel R, Kumar Ashok

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University P.O. Box 2457, Riyadh, Saudi Arabia ; Department of Cell Biology, National Research Centre (12622) Cairo, Egypt.

Department of Hormones, Medical Research Division, National Research Centre (12622) Cairo, Egypt.

出版信息

Int J Clin Exp Pathol. 2015 Aug 1;8(8):8821-31. eCollection 2015.

Abstract

IQGAPs genes play critical role in either induction or suppression of cancer and its progression, however the relationship between Ras genes and these genes are still unclear. In this study, we tried to understand the mechanistic action of IQGAPs genes and its correlation with Ras genes in mouse hepatic cancer model. The genetic expressions of IQGAP1, IQGAP2, IQGAP3, Hras, Kras, Nras, Mras, Caspase3, and BAX were followed in both hepatocellular carcinoma and normal liver cells of Balbc mice. Genotoxic agent diethylnitrosamine (DEN)-induced hepatic cancer model was induced in male mice and recorded the occurrence of hepatocellular carcinoma by morphological and histological changes in the liver. It was observed that mRNA expressions of IQGAP1, Hras, Kras, Nras, Mras, Caspase3, and BAX genes were highly elevated in hepatocellular carcinoma cells when compared with normal liver cells, additionally their expressions increased by concentrating the dose of DEN. While, the expressions of IQGAP2 and IQGAP3 were significantly decreased in hepatocellular carcinoma cells when compared with normal liver cells, as well as their expressions decreased more with increasing the dose of DEN. It was concluded from this study that IQGAP1 has a strong signaling relationship with Ras genes in induction of cancer and it is considered as a key gene for induction or suppression of the hepatocellular carcinoma.

摘要

IQGAPs基因在癌症的诱导或抑制及其进展中发挥着关键作用,然而Ras基因与这些基因之间的关系仍不清楚。在本研究中,我们试图了解IQGAPs基因在小鼠肝癌模型中的作用机制及其与Ras基因的相关性。在Balbc小鼠的肝细胞癌和正常肝细胞中追踪IQGAP1、IQGAP2、IQGAP3、Hras、Kras、Nras、Mras、Caspase3和BAX的基因表达。用基因毒性剂二乙基亚硝胺(DEN)诱导雄性小鼠建立肝癌模型,并通过肝脏的形态学和组织学变化记录肝细胞癌的发生情况。观察到与正常肝细胞相比,IQGAP1、Hras、Kras、Nras、Mras、Caspase3和BAX基因的mRNA表达在肝癌细胞中高度升高,此外,随着DEN剂量的增加,它们的表达也增加。而与正常肝细胞相比,IQGAP2和IQGAP3在肝癌细胞中的表达显著降低,并且随着DEN剂量的增加,它们的表达降低得更多。本研究得出结论,IQGAP1在癌症诱导中与Ras基因有很强的信号关系,并且它被认为是诱导或抑制肝细胞癌的关键基因。

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