| | | 乳腺癌中STAT3对HSP27和c
| | 中医学论文【关键词】 乳腺癌
Regulating role of STAT3 to HSP27 and cMYC expression in breast cancer
【Abstract】 AIM: To investigate the regulating role of signal transducer and activator of transcription 3 (STAT3) to 27 ku heat shock protein (HSP27) and cMYC expression in breast cancer. METHODS: Expressions of STAT3, HSP27 and cMYC were examined in primary breast infiltrating duct carcinoma tissues of 51 patients using immunohistochemistry. Correlations between STAT3 expression and HSP27 or cMYC expression were analyzed with statistic method. After the transfection of MDAMB435S human breast carcinoma cells with STAT3 decoy oligodeoxynucleotides (Decoy ODNs), expressions of HSP27 and cMYC of MDAMB435S were semiquantified by Western blot, the apoptosis and the cell cycle distribution of MDAMB435S cells were analyzed with flow cytometry and proliferation of MDAMB435S cells was analyzed by MTT assay. RESULTS: In primary breast infiltrating duct carcinoma tissues, STAT3 expression was correlated positively with HSP27 expression and cMYC expression respectively (rs=0.454, P=0.001; rs=0.541, P=0.000). As the result of STAT3 inhibition by STAT3 Decoy ODNs in MDAMB435S cells, expressions of HSP27 and cMYC were markedly reduced, which was consistent with STAT3 activation reduction (Both P<0.01). The cell cycle progression of MDAMB435S cells was significantly inhibited at G0/G1 phase, the apoptosis of those cells was augmented and their proliferation was inhibited (P<0.01). CONCLUSION: Constitutively activated STAT3 may upregulate HSP27 and cMYC expression to inhibit breast cancer cell apoptosis and to facilitate their proliferation, thus leading to the malignancy of breast cancer cells.
【Keywords】 breast neoplasms; oncogenes; signal transducer and activator of transcription 3; heat shock proteins 27; genes, cMYC
【摘要】 目的中医学论文：研究人乳腺癌组织中信号转导和转录激活因子3(STAT3)对热休克蛋白27（HSP27）和cMYC的中医学论文调控作用. 方法：应用免疫组化检测51例人乳腺癌组织STAT3，HSP27，cMYC蛋白的表达，分析他们的相互关系及与临床预后相关指标的关系. 在体外应用诱骗寡核苷酸（Decoy ODNs）抑制乳腺癌细胞MDAMB435S STAT3活性，Western blot检测MDAMB435S细胞HSP27，cMYC蛋白表达，MTT检测肿瘤细胞增殖力，FCM检测MDAMB435S细胞周期和凋亡. 结果：在人乳腺浸润性导管癌组织中，STAT3的表达与HSP27和cMYC表达均成正相关（rs=0.454,P=0.001；rs=0.541，P=0.000）. 使用Decoy ODNs抑制人乳腺癌细胞株MDAMB435S STAT3活性能使其HSP27和cMYC表达明显下调（P均<0.01），并使细胞阻滞于G0/G1期，凋亡增加，细胞增殖能力下降（P<0.01）. 结论：STAT3表达可能通过上调HSP27和cMYC的表达，抑制乳腺癌细胞的凋亡和促进其增殖，从而有利于乳腺癌进展并使其恶性程度增高.
【关键词】 乳腺肿瘤；癌基因；信号转导和转录激活因子3；热休克蛋白27；基因，cMYC
0引言
信号转导和转录激活因子3(signal transducers and activators of transcription 3, STAT3)通过调节下游基因的表达在肿瘤细胞增殖和分化过程中起着重要作用，但到目前为止，对STAT3调节的靶基因所知甚少. 我们通过检测人乳腺癌标本中STAT3，热休克蛋白27（heat shock protein 27 ku, HSP27），cMYC蛋白的表达和通过诱骗寡核苷酸(decoy oligodeoxynucleotides, Decoy ODNs)抑制人乳腺癌细胞株MDAMB435S STAT3活性，检测其HSP27，cMYC蛋白表达，探讨在乳腺癌中，STAT3的过度激活对HSP27和cMYC的表达的调节作用.
1材料和方法
1.1材料
组织标本为重庆医科大学第一医院200110/200202经病理学诊断为女性乳腺浸润性导管癌标本51例，年龄34~61岁，术前未经化疗. 乳腺癌细胞株MDAMB435S（重庆医科大学第一医院器官移植研究室保存），RPMI 1640（Hyclone公司），新生小牛血清（杭州四季青公司）. 阳离子脂质体转染试剂lipofenctin（Invitrogen公司）. Decoy ODNs为能够特异地与磷酸化的STAT3和STAT1形成的同源或异源二聚体结合的sis诱导因子(SIF)复合物结合的M67基序，sense序列为5′TGCATTTCCCGTAAATCT3′， antisense序列为 5′AAGATTTACGGGAAATGC3′，全部经过硫代修饰，Mismatch Decoy ODNs(MDecoy ODNs) 为Decoy ODNs下划线部分碱基重排，FITCDecoy ODNs的sense 和antisense序列同Decoy ODNs，sense链5′端标记FITC，由上海Sangon合成. 兔抗鼠STAT3多抗，兔抗鼠HSP27多抗，兔抗鼠βactin多抗，HR标记的羊抗兔Ig多抗（Santa cruz公司）. T7核苷酸激酶（Promega公司），Poly(dIdC)・Poly(dIdC)（Amersham公司），γ32PATP（北京福瑞公司），Western blot增强放光试剂（北京中山公司）.
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