| ObjectiveThe tumor is the formation of neoplasm with abnormal growth of cells which tend to proliferate in an uncontrolled way under the various factors. The malignant tumor is a disease that seriously harmful to human health, many tumors are diagnosed at late stage for lack of specifically early diagnose, so the 5 years survival rate is still very low. To explore the molecular mechanism of carcinogenesis and progress might improve early diagnosis and treatment, and might also help to find new prognostic factors.Rencently research have shown that the tumorigenesis stem from not only genetic but epigenetic alterations. The former refers to the changes in gene expression with the alteration in the gene sequences, while the latter means that the heritable, reversible changes in gene expression but without any alteration in nucleotide sequence. Histone modification is an important component of epigenetics, the histone acetylation and deacetylation modification is mostly studied recently, the unbalance of histone acetylation modification is associated with the tumorigenesis. But the relation between histone modification and cell signaling pathways remains unclear.In this research, we first investigate the expression of H3K4 AC and H3K27 AC in gastric carcinoma use immunohistochemistry, and then detect the expression level of H3K4 AC and H3K27 AC in different cancer cell lines by regulating the Wnt/β-catenin and PI3K/Akt signaling pathways, which is able to provide the basis for neoplasms diagnosis and treatment. Methods The study was divided into 3 sections:In the first part: Using tissue microarray techniques and immunohistochemistry assay to survey the expression of H3K4 AC and H3K27 AC in 45 different graded gastric carcinoma tissues and corresponding 45 para-carcinoma tissues and 10 normal gastric mucosa tissues.In the second part: Using the Western blot to survey the expression level of H3K4 AC and H3K27 AC in gastric tumor cells MGC-803, BGC-823, glioma tumor cells U87, U87 EGFRv III, hepatoma cells Hep-3B, colonic cancer cells Caco-2 when the activity of Wnt/β-catenin signaling pathway is changed.In the third part: Using the Western blot to survey the expression level of H3K4 AC and H3K27 AC in gastric tumor cells MGC-803, BGC-823, glioma tumor cells U87, U87 EGFRv III, hepatoma cells Hep-3B, colonic cancer cells Caco-2 when the activity of PI3K/Akt signaling pathway is changed.ResultsThe first part: Immunohistochemistry results show that the expression of H3K4 AC and H3K27 AC in gastric carcinoma tissue is obviously lower than the normal gastric mucosa, and with the increasing of pathologic grade, the H3K4 AC and H3K27 AC express down-regulated, and the result have statistical significance(P<0.05).The second part: Western blot results show that the H3K4 AC and H3K27 AC express descending in all of the cell lines when we treat the cells with the inhibitor of the Wnt/β-catenin signaling pathway FH535, and the descending is more obviously with the increase of the drug concentration and action time. This trend is more evidently when the gastric cell lines were pre-treated with the TGF-β followed by the FH535. The H3K4 AC and H3K27 AC expression up-regulated when the cells treated with the activor of the signaling pathway Wnt3 a.The third part: Western blot results show that the H3K4 AC and H3K27 AC express descending in all of the cell lines when we treat the cells with the inhibitor of the PI3K/Akt signaling pathway LY294002, and the descending is more obviously with the increase of the drug concentration and action time, and the expression up-regulated when the cells treated with the activor of the signaling pathway EGF. ConclusionThe H3K4 AC and H3K27 AC is lower-expression in gastric carcinoma tissues, and is positive correlated with the pathological degree, this shows that the histone acetylation associated with the malignant degree of gastric cancer to a certain extent. The change of the Wnt/β-catenin and PI3K/Akt signaling pathway activity can regulate the expression of H3K4 AC and H3K27 AC in cancer cells, it means that histone acetylation modification have relation with the cell signaling pathway.The expression of histone acetylation modification in various cancer cells can be transformed by regulating the two signaling pathways, and then affect the development and progression of carcinomas, offers a new direction for the treatment of tumors. |
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