RASSF10 Suppresses Colorectal Cancer Growth by Activating P53 Signaling and Sensitizes Colorectal Cancer Cell to Docetaxel
Objective: To further understand the methylation status, expression, function, and mechanism of RASSF10 in colorectal cancer.Method: Eight colorectal cancer cell lines, 89 cases of primary colorectal cancer, and 5 cases of normal colorectal mucosa were involved in this study.Methylation specific PCR, western blot, colony formation, siRNA, gene expression array, and xenograft mice were employed.Results: Loss of RASSF10 expression and complete methylation were found in LOVO, RKO, and HCT116 cells.Expression or reduced expression and partial methylation were found in LS180, DLD1, HT29, SW480, and SW620 cells.Restoration or increased expression of RASSF10 was found in these colorectal cancer cells by 5-aza-2”-deoxycytidine treatment.RASSF10 was methylated in 60.7％ (54/89) of primary colorectal cancer samples.Methylation was associated with tumor stage (P ＜ 0.05) and metastasis (P ＜ 0.05).Re-expression of RASSF10 inhibited cell proliferation and induced apoptosis and G2/M phase arrest in RKO and HCT116 cells.HCT116 cells tumor xenograft was suppressed by RASSF10.Reduced expression of MDM2 was revealed by comparison of gene expression profile in RASSF10 expressed and unexpressed RKO cells.The result was confirmed by RT-PCR and western blot.RASSF10 activated P53 signaling in RKO and HCT116 cells after UV exposure.RASSF10 sensitized RKO and HCT116 cells to docetaxel.Conclusions: RASSF10 is frequently methylated in human colorectal cancer and the expression is regulated by promoter region hypermethylation.Methylation of RASSF10 is associated with late tumor stage and metastasis.RASSF10 suppresses human colorectal cancer growth by activating P53 signaling in colorectal cancer.RASSF10 sensitizes colorectal cancer to docetaxel.
郭静 杨雅阁 杨云生 詹启敏 James G.Herman Malcolm V.Brock 张炳勇 郭明洲
中国人民解放军总医院消化内科 中国人民解放军总医院消化内科;郑州大学第一附属医院 中国医学科学院 Johns Hopkins University 河南省人民医院
国内会议
第八届中国肿瘤内科大会、第三届中国肿瘤医师大会暨中国抗癌协会肿瘤临床化疗专业委员会2014年学术年会
北京
英文
504-504
2014-07-02（万方平台首次上网日期，不代表论文的发表时间）