4) Furthermore, more times

4). Furthermore, more times CYC202 mw treated with MNNG/PMA, more increase of acetylated histone H3 was observed. This indicated that MNNG/PMA treatment leaded to increased level of acetylated histone H3, and thus altered gene expression. Figure 4 Western blot analisis of acetylated histone H3 in IEC-6 cells. Total protein (30 μg per lane) was resolved on SDS-polyacrylamide gel and transferred onto a nitrocellulose membrane and incubated with anti-acetylated histone

H3 and anti-GAPDH antibodies. The bands were visualized by using the enhanced chemiluminescence system. The relative abundances of acetylated histone H3 was normalized by that of GAPDH. Lane1: normal IEC-6 cells; Lane2: IEC-6 cells treated with MNNG/PMA for 6 times; Lane2: IEC-6 cells treated with MNNG/PMA for 12 times. Discussions Substantial advances in our understanding during the past decades have led to a complete understanding of the role of both environmental and genetic factors in colorectal cancer pathogenesis. It has been well PS-341 manufacturer demonstrated that the its development and progress are associated with deregulation of many genes, as well as mutational activation of oncogenes and loss of function of tumor suppressor genes [22]. And its tumorigenesis is also a process of multistage of hit. As a multiple factor disease, complex genetic pathways are involved in

colorectal cancer. The most troublesome bewilderment is that different profile of mutant

genes leads to the same clinical phenotype. So the detailed find more molecular mechanism of colorectal cancer has not been fully understood. Many important biological processes were involved in transformation and tumorigenesis, including Aldol condensation cell cycle control, DNA damage repair, cell apoptosis and signal transduction. The rat Oligo GEArray microarray profiles the expression of 113 genes representative of the six biological pathways involved in transformation and tumorigenesis. It has been applied in many experiments [23, 24]. Our results showed that most of the six biological pathways were involved in transformation of IEC-6 cells. This indicated that transformation were the consequence of multiple deregulations of genes. Among the genes differentially expressed, some were also found altered in tumor by other researchers. Our experiment showed that c-fos was up-regulated greatly in transformed cells. Many experimental and clinical data indicated that c-fos expression plays a role in the progression of several types of carcinomas [25]. Increased expression of c-fos was also found to be associated with metastasising ability of metastatic colorectal cancer by cDNA macroarray analysis [26]. Another gene increased greatly in transformed IEC-6 cells was Ifna1, which played an important role in angiogenesis of tumor. Ifna1 plays a pivotal role not only in antiviral immunity but also in the surveillance of cancer development.

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