Chang Liang-Che, Fan Chung-Wei, Tseng Wen-Ko, Chein Hui-Ping, Hsieh Tsan-Yu, Chen Jim-Ray, Hwang Cheng-Cheng, Hua Chung-Ching
Department of Pathology, Chang Gung Memorial Hospital, Keelung & Chang Gung University, 222 Maijin Road, Keelung 204, Taiwan, Republic of China.
Division of Colon & Rectal Surgery, Chang Gung Memorial Hospital, Keelung & Chang Gung University, 222 Maijin Road, Keelung 204, Taiwan, Republic of China.
Biomark Med. 2017 Dec;11(12):1103-1111. doi: 10.2217/bmm-2017-0107. Epub 2017 Oct 20.
Thioredoxin can reduce the cysteine group of Keap1 which could induce proteasome degradation of Nrf2, PGAM5 and Bcl-xL. Nrf2 regulates redox balance and Bcl-xL is anti-apoptotic and both are important in tumor progression.
The protein levels of Keap1, thioredoxin, PGAM5 and Bcl-xL in the normal and tumor tissues of 64 subjects with colorectal cancer (CRC) were determined by western blot.
The tumor had higher Keap1 but lower PGAM5s and Bcl-xL protein expression than the normal tissue. The ratio of thioredoxin/Keap1 protein level in the normal (OR: 0.12; 95% CI: 0.02-0.83) or tumor tissue (OR: 0.17; 95% CI: 0.03-0.89) was a negative predictor for distant metastasis in CRC.
Keap1-mediated degradation of PGAM5 and Bcl-xL may be active in CRC. The ratio of thioredoxin/Keap1 protein level may be useful for suggesting distant metastasis in CRC.
硫氧还蛋白可还原Keap1的半胱氨酸基团,而Keap1可诱导Nrf2、PGAM5和Bcl-xL的蛋白酶体降解。Nrf2调节氧化还原平衡,Bcl-xL具有抗凋亡作用,二者在肿瘤进展中均起重要作用。
采用蛋白质印迹法检测64例结直肠癌(CRC)患者正常组织和肿瘤组织中Keap1、硫氧还蛋白、PGAM5和Bcl-xL的蛋白水平。
与正常组织相比,肿瘤组织中Keap1蛋白表达较高,但PGAM5和Bcl-xL蛋白表达较低。正常组织(OR:0.12;95%CI:0.02-0.83)或肿瘤组织(OR:0.17;95%CI:0.03-0.89)中硫氧还蛋白/Keap1蛋白水平比值是CRC远处转移的负性预测指标。
Keap1介导的PGAM5和Bcl-xL降解在CRC中可能较为活跃。硫氧还蛋白/Keap1蛋白水平比值可能有助于提示CRC的远处转移。