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. 2015 Aug 1;8(8):8821-31.
eCollection 2015.

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

Affiliations

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

Khairy M A Zoheir et al. Int J Clin Exp Pathol. .

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.

Keywords: DEN; IQGAP1; IQGAPs; hepatocellular carcinoma; ras.

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Figures

Figure 1
Figure 1
Body and liver weights in Balbc mice.
Figure 2
Figure 2
Incidence of histopathological changes of the liver in Balbc mice.
Figure 6
Figure 6
Morphology of Balbc mice liver treated by DEN (A) is normal control and (B) is treated by 75 mg/kg DEN 8 weeks.
Figure 7
Figure 7
Formation of altered hepatocellular foci (AHF) and tumors in the liver of Balbc mice treated with diethylnitrosamine. (A-D) The lesions of a hepatocellular adenoma (C and D), a cholangioma (D), and a hemangioma (C-F). (H) Typical basophilic, clear, and eosinophilic AHF, along with a biliary cyst. (A and B) Hematoxylin and eosin stained.
Figure 3
Figure 3
(A, B) The expression of IQGAP genes in liver tissues of different treated groups after 4 weeks (A) and 8 weeks (B).
Figure 4
Figure 4
(A & B) The expression of Ras genes in liver tissues of different treated groups after 4 weeks (A) and 8 weeks (B).
Figure 5
Figure 5
(A & B) The expression of Casp3 and BAX genes in liver tissues of different treated groups after 4 weeks (A) and 8 weeks (B).

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