候选抑癌基因syk启动子甲基化与乳腺癌发生和转移的关系

目的　探讨脾酪氨酸激酶 (spleentyrosinekinase ,syk)基因启动子甲基化与乳腺癌发生、发展过程的关系。方法　采用逆转录 聚合酶链反应 (RT PCR)检测了 4 0例乳腺癌组织、癌旁组织及15例乳腺纤维瘤组织中sykmRNA的表达 ,同时用甲基化特异性PCR(MSP)方法检测syk基因启动子甲基化情况。结果　 4 0例癌旁组织、乳腺纤维瘤组织均检测到syk基因的表达 ,乳腺癌组织有 9例检测到syk基因的表达 ,syk基因在乳腺癌组织中表达率显著降低 (P <0 .0 5 )。癌旁组织及乳腺纤维瘤组织未发现有syk基因启动子的甲基化 ,4 0例乳腺癌组织中有 17例检测到syk基因启动子的甲基化 ,癌组织syk基因启动子甲基化率显著增高 (P <0 .0 5 )。有淋巴结转移的 18例乳腺癌组织中 ,有 14例syk基因启动子甲基化 ,有淋巴结转移的syk基因启动子甲基化显著高于无淋巴结转移组 (P <0 .0 5 )。结论　syk基因启动子甲基化是导致syk基因失活的原因之一 ,syk基因启动子的甲基化可能与乳腺癌的发生、转移相关。

Hypermethylation of syk gene in promoter region is associated with oncogenesis, metastasis of breast carcinoma

Objective To investigate the relationship between methylation of syk (spleen tyrosine kinase)gene in promoter region and oncogenesis, metastasis in breast carcinoma. Methods Using RT-PCR technique, specimens from 40 breast cancer patients(tumor tissues, adjacent normal tissues), 15 fibroadenoma were detected for their expression of the syk gene. Meanwhile, Methylation-specific PCR was used to detect methylation of syk promoter region. Results The expression of syk gene were detected in normal breast tissues and fibroadenoma samples, 9 out of 40 breast carcinoma samples were found the expression of syk mRNA, syk expression in breast carcinoma was lower than that in adjacent normal tissues and fibroadenoma samples. No methylation of syk promoter was found in adjacent normal tissues and fibroadenoma samples, 17 cases in 40 breast carcinoma patients(42.5%) were detected hypermethylation of syk gene in promoter region, the rate of methylation of syk promoter in breast carcinoma was higher than that of in adjacent normal tissues( P <0.05). In 18 cases with lymph node metastasis, 14 were found with syk promoter methylation. A significant difference was noted between two groups( P <0.05). Conclusion Hypermethylation leads to lose of the syk gene expression in human breast carcinoma. Methylation of syk promoter may be correlated to oncogenesis, metastasis of breast carcinoma.