The Role Of The NF-kappa B Signal Transduction Pathway In H-ras12V Transgenic Mice Liver Tumorigenesis

The causes of liver cancer are various, the process is complicated, and its mechanisms remain unclear. Invitro studies have shown that the Ras signaling pathway play an important role in the occurrence anddevelopment of liver cancer. We have used albumin promoter to induce the Ras oncogene specificityexpression in liver cells and have successfully established the Ras transgenic mouse model of liver cancerr.Recent years, researches showed that the nf-kappa B signal transduction pathways has a very importantrelationship withthe occurrence, development,resistance to apoptosis, invasion and metastasis of the tumor[1].This study investigated the active state of NF-kappaB signal transduction pathway in the H-ras12V turntransgenic mice, and the interaction of the Ras signaling pathway and NF-kappaB signal transduction pathwayin liver tumor. Liver tissue of the normal wild-type mice was obtained as controlto study the H-ras12V turntransgenic mouse liver tumor tissue and tumor surrounding tissue. Total RNA was extracted from collectedliver tissue and mRNA expression levels were tested using fluorogenic quantitative PCR to detect thedownstream key genes of NF-kappaB signal transduction pathway; Total protein and nuclear protein wereextracted in the liver tissue for western blot to detect downstream key protein expression levels and activationstate of NF-kappaB signal transduction pathway and the nucleus of the expression level of p65and p52.Results:(1) All H-ras12v transgenic mice have liver tumors in8monthsold,12v and H-rasgenetically modified female mice have liver tumors until14monthsold.(2) In transgenic mice group, the Rassignaling pathway activation, promote higher downstream of the expression of PI3K, AKT phosphorylationlevels, so as to activate the nf-kappa B signal transduction pathway. The nf-kappa B signal transductionpathway is activated, activating protein into the nucleus to regulate the target genes of transcription[2].Genetically modified female mice, the Ras signaling pathway activation, promote higher downstream of theexpression of PI3K, and genetically modified female AKT phosphorylation level in tumor tissues is reduced,the nf-kappa B signal transduction pathway is suppressed.Conclusion: based on the above experimental results, the NF-kB the activation of signal transductionpathways plays an important role in the H-ras12V transgenic mice tumor development., The continuedactivation of the NF-kB pathway may promotes the occurrence of liver tumors in H-Ras12V transgenic mice;and genetically modified female rats were able to bypass the NF-kB pathway inhibition, induce liver cancerthrough other channels.