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Abstract
The IGF-1R signalling pathway can positively regulate cell-cycle progression and thus play a critical role in cancer development. Although recent studies provide sufficient evidence supporting the functional importance of IGF-1R in cancer, the prognostic significance of IGF-1R expression levels to colorectal cancer (CRC) remains obscure. Expression of IGF-1R mRNA was examined in paired samples of CRC and adjacent normal mucosa, as well as in CRC patients' venous blood. We also investigated the effect of two monocytes stimulus—C3bgp and LPS on induced mRNA of IGF-1R from normal and colorectal human monocytes. The role of a member of MAPK signal transduction pathways—JNK in IGF-1R expression was assessed. The expression of IGF-1R mRNA was measured by relative RT-PCR. The results demonstrated that expression of IGF-1R mRNA in venous blood from CRC was down-regulated compared to venous blood from healthy donors (1.426 vs. 0.645; p=0.024). Mean IGF-1R mRNA level was found to be approximately 5.8 fold higher in tumour tissue compared to adjacent normal mucosa (p=0.02). Strong IGF-1R mRNA expression was found for early stages of CRC. The results showed that both stimuli used, strongly up-regulated mRNA expression for IGF-1R in CRC monocytes, then in monocytes from healthy donors. The highest level of IGF-1R expression was detected after C3bgp stimulation, regardless of JNK inhibitor presence. The significance for increasing expression of IGF-1R was observed for early CRC when patients were divided according to the tumour stage. We can conclude that downregulation of mRNA expression of IGF-1R in peripheral blood cells and stimulated monocytes from patients with advanced stages of colorectal cancer are a hallmark of tumour progression and can be used as a prognostic factor.
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