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Expression of genes of tumor necrosis factor -α and its receptors in colon cancer Caco-2 cells treated with inositol hexaphosphate |
| Beata Parfiniewicz , Krzysztof Cholewa , Małgorzata Kapral , Ludmiła Węglarz |
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Departament of Biochemistry, Medical University of Silesia, Narcyzow 1, Sosnowiec 41-200, Poland |
| Abstract |
Pathological processes accompanying cancer colon diseases are associated with aberrant expression of many hormones, growth factors and cytokines, including tumor necrosis factor alpha (TNF-α). TNF-α is a pleiotropic cytokine which is involved in numerous processes such as cell death and development, oncogenesis and immune, inflammatory, and stress response. It is intriguing that the cytokine possesses both growth stimulating properties and growth inhibitory properties. In people TNF-α is encoded by gene situated on chromosome 6. Most of the biological effects of TNF-α are mediated through the TNFR1 and TNFR2 receptors which are expressed on all somatic cells. Recently several groups have examined the transcriptional regulation of TNF-α and its receptors by various inducers, such as virus, LPS, phorbol 12-myristate 13-acetate (PMA), IL-2, IFN-α. Scientists have taken an interest in phytic acid. It has been reported that phytic acid (inositol hexakisphosphate; IP6), a natural ingredient of high fiber diet, has an anticancer role. Yet very little is known about the signal transduction mechanisms involved in mediating the anti-tumor growth observed in carcinoma cells, although this is now an area of intensive research activity. Additionally, it was reported that IP6 present in the intestinal milieu may exert immunoregulatory effects on colonic epithelium under physiological conditions or during microbe-induced infection/inflammation. The influence of phytic acid on TNF-α and its receptors genes’ expression in Caco-2 cell line has not been a subject of investigation, so far. In the present study, we investigated whether and how IP6 affects the transcriptional activation of TNF-α, TNFR1 and TNFR2 genes in human colon cancer cells, by analyzing the amount of the corresponding mRNA produced in the cells as a function of time of treatment (1; 6; 12 and 24 hours) and IP6 concentration (1; 2.5; 5 mM). Real time QRT-PCR based on TaqMan methodology was applied to analyze quantitatively the transcript levels of these genes. The results showed that the expression of TNF-α and TNFR1 but not that of TNFR2 changed in time in control cells. IP6 at 1 mM dose reduced mRNA level of TNF-α at 6, 12 and 24 h and caused statistically significant increase in TNFR2 at 1h. Transcriptional activity of TNF-α has been observed to decrease under treatment of cells with 2.5 mM IP6 for 12 h. The highest IP6 dose (5 mM) evoked the stimulation of TNF-α gene transcription at 1 and 6 h followed by its decline after 12 h treatment. There were no quantitative changes in the TNFR1 gene expression in cells exposed to 1 mM IP6 for 1,6, 12 and 24 h. At 6 and 12 h the levels of TNFR1 transcript in cultures with 2.5 and 5 mM IP6 exceeded those of control cells, whereas the TNFR2 mrna levels demonstrated quite opposite tendency. IP6 seems to modulate the expression of the studied genes at transcriptional level in Caco-2 cells. |
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Presentation: Poster at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum E, by Beata ParfiniewiczSee On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego Submitted: 2007-04-30 16:50 Revised: 2009-06-07 00:44 |