背景与目的:前期研究发现驱动蛋白样DNA结合蛋白(kinesin—like DNA—binding protein,Kid)的编码基因kinesin—like4(KNSIA)mRNA在乳腺癌的淋巴结转移癌中较其配对的原发癌表达下调。本研究目的是证实KNSL4 mRNA表达水平与乳腺癌临床病理因素及转移和预后的关系,并考察其作为转录调节因子与c-erbB-2蛋白表达的关系,以探讨其促进肿瘤细胞转移的可能机制。方法:采用实时定量RT-PCR方法检测108例乳腺原发癌组织中KNSIA mRNA表达,分析其与临床病理因素及转移和预后的关系;免疫组织化学方法检测其中76例乳腺癌组织中c-erbB-2蛋白表达,分析KNSIAmRNA表达与c—erbB-2蛋白表达的关系。结果:KNSL4 mRNA的平均相对表达量在临床分期Ⅲ~Ⅳ期组低于临床Ⅰ-Ⅱ期组(P〈0.001);转移淋巴结数〉3个组低于0~3个组(P〈0.01);在ER和PR阴性组均低于阳性组,但差异无显著性(P=0.216,0.065);2年随访有远处转移组较无远处转移组下调,但因随访时间短尚无法进行统计学分析;3例双乳癌KNSIA mRNA的平均相对表达量较非双乳癌且无远处转移的病例下调68.8%。KNSIA mRNA表达在c—erbB-2阳性组低于阴性组(P〈0.01)。结论:KNSIA mRNA在乳腺原发癌中的表达水平与乳腺癌的预后有关,并可能通过促进c—erbB-2基因转录和蛋白表达提高乳腺癌细胞的转移能力。
BACKGROUND & OBJECTIVE & Previous screening of breast cancer metastasis-related genes found that the mRNA level of kinesin-like 4 (KNSL4) gene is down-regulated in metastatic lymph nodes as compared with the paired primary breast cancer. This study was to clarify the correlations of KNSL4 mRNA expression to metastasis and prognosis of breast cancer, and explore the correlation of KNSL4 expression to c-erbB-2 expression to explore potential mechanisms of promoting metastasis by KNSL4. METHODS:Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify the mRNA level of KNSL4 in 108 specimens of primary breast cancer. The correlations of KNSL4 mRNA level to metastasis and prognosis of the 108 cases were analyzed. Immunohistochemistry was used to assess c-erbB-2 protien expression in 76 out of the 108 cases, and the correlation of KNSL4 expression to c-erbB-2 expression was analyzed. RESULTS: The mRNA level of KNSL4 was significantly lower in the cases at stages Ⅲ -Ⅳ than in the cases at stages Ⅰ - Ⅱ (P〈0.001), significantly lower in the cases with more than 3 metastastic lymph nodes than in the cases with 0-3 metastastic positive lymph nodes (P〈0.01), slighly lower in the cases with negative estrogen receptor or prognesterone receptor than in the cases with positive receptors (P〉0.05), lower in the 6 cases with distant metastasis than in the rest cases without distant metastasis within 24 month follow up, lower in the 3 cases with bilateral breast cancer than in other cases with unilateral breast cancer, and significantly lower in c-erbB-2- positive group than in c-erB-2-negative group (P〈0.01). CONCLUSIONS:The down-regulation of KNSL4 mRNA level is correlated to prognosis of primary breast cancer. It may enhance metastatic ability of breast cancer cells through promoting c-erbB-2 transcription and translation.