膀胱癌组织中Wnt拮抗因子分泌型卷曲相关蛋白1甲基化和异常表达的意义
Methylation and aberrant expression of Wnt antagonist SFRP1 in bladder cancer
目的 探讨Wnt拮抗因子分泌型卷曲相关蛋白1(SFRP1)甲基化和表达在膀胱癌发病机制中的作用. 方法 采用甲基化特异性聚合酶链反应检测人膀胱癌细胞株T24、5637和SCaBER及45例膀胱癌组织和对应癌旁正常组织的SFRP1基因甲基化状态,蛋白质印迹方法检测SFRP1蛋白表达. 结果 SFRP1在膀胱癌细胞株T24和5637中呈现甲基化状态,而SCaBER细胞未检出SFRP1甲基化.将去甲基化试剂5’-氮杂-脱氧胞苷酸(1μg/ml)加入发生甲基化的膀胱癌细胞株T24和5637后,细胞SFRP1 mRNA和蛋白出现表达.45例膀胱癌组织中SFRP1甲基化表型28例(62.2%),癌旁正常组织6例(13.3%),组间频率差异有统计学意义(P<0.01). 结论 SFRP1甲基化及表达下调可能参与了膀胱癌的发病过程.
更多Objective To measure the expression of SFRP1 in bladder cancer and explore the corresponding mechanism,in order to study the roles of SFRP1 in the pathogenesis of bladder cancer.Methods SFRP1 mRNA was detected by RT-PCR.Methylation status of SFRP1 was detected by methylation specific PCR.SFRP1 protein was determined by Western blotting.Results SFRP1 was methylated in bladder cancer cell lines T24 and 5637,not in SCaBER.SFRP1 mRNA and protein were detected in SCaBER,but not in T24 and 5637.Six hours after treating T24 and 5637 with 5'-aza-deoxycytidine,both T24 and 5637 expressed SFRP1 mRNA and protein.In 45 bladder cancers,methylation of SFRP1 was detected in 28 (62.2%).In matched cancer adjacent tissues,6 (13.3%) were found with SFRP1 methylation.The methylation rate in bladder cancers was significant higher than that in matched cancer adjacent tissues (P < 0.01).Conclusions SFRP1 is downregulated in some bladder cancers due to methylation.SFRP1 methylation and aberrant expression may be involved in the pathogenesis of bladder cancers.
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