Ueno M, Matsutani Y, Nakamura H, Masutani H, Yagi M, Yamashiro H, Kato H, Inamoto T, Yamauchi A, Takahashi R, Yamaoka Y, Yodoi J
Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Sakyo, Japan.
Immunol Lett. 2000 Dec 1;75(1):15-20. doi: 10.1016/s0165-2478(00)00284-4.
Expression of thioredoxin (TRX), a dithiol-reducing enzyme, and mutations of p53 have been detected in various cancer tissues. We recently reported that TRX-dependent redox regulation plays a crucial role in DNA binding activity of p53. In this study, we investigated the possibility of functional association between TRX and p53 in breast cancer. First, we examined the expression of TRX and mutated p53 in 100 primary breast cancer tissues by immunohistochemistry. Expression of TRX was detected in cases of 84/100 (84%) and expression of p53, which means existence of mutated p53, in cases of 63/100 (63%). TRX positive cases was 89% (56/63) in mutant p53 positive cases. Next, we examined the expression of TRX and p53 in breast cancer cell line MCF-7 cells after CDDP treatment or irradiation. CDDP treatment or irradiation augmented expression of TRX and p53 in MCF-7 cells by western blotting. Immunofluorescence cell analysis by confocal microscopy showed that CDDP treatment induced translocation of TRX into nuclei. These results suggest the possible association of TRX with p53-dependent function including DNA repair in breast cancer.
在多种癌症组织中已检测到二硫醇还原酶硫氧还蛋白(TRX)的表达以及p53的突变。我们最近报道,TRX依赖的氧化还原调节在p53的DNA结合活性中起关键作用。在本研究中,我们调查了乳腺癌中TRX与p53之间功能关联的可能性。首先,我们通过免疫组织化学检测了100例原发性乳腺癌组织中TRX和突变型p53的表达。100例中有84例(84%)检测到TRX表达,100例中有63例(63%)检测到p53表达,即存在突变型p53。在突变型p53阳性病例中,TRX阳性病例占89%(56/63)。接下来,我们检测了顺铂(CDDP)处理或照射后乳腺癌细胞系MCF-7细胞中TRX和p53的表达。通过蛋白质印迹法检测发现,CDDP处理或照射可增强MCF-7细胞中TRX和p53的表达。共聚焦显微镜进行的免疫荧光细胞分析表明,CDDP处理可诱导TRX转位至细胞核。这些结果提示TRX可能与乳腺癌中包括DNA修复在内的p53依赖性功能相关。