Hou Ming Feng, Lin Shwu Bin, Yuan Shyng Shiou F, Tsai Shih Meng, Wu Szu Hua, Ou-Yang Fu, Hsieh Jan Shih, Tsai Kun Bow, Huang Tsung Jen, Tsai Li Yu
Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Clin Chim Acta. 2003 Aug;334(1-2):137-44. doi: 10.1016/s0009-8981(03)00196-7.
This study investigated the role of nuclear factor-kappa B (NF-kappaB) activity in human breast cancer with overexpression of HER-2/neu oncoprotein, as well as its role on expression of different histological grades of cancer cells taken from Taiwanese breast cancer patients.
Specimens were collected from 82 female breast cancer patients. The HER-2/neu oncoprotein was measured by immunohistochemistry. NF-kappaB activity expression was assessed by the electrophoretic mobility shift assay, and confirmed by the supershift technique using anti-P65 antibody in both breast cancer tissue and the adjacent normal tissue. The histological grades were measured by Modified Bloom-Richardson Grading Scheme.
Of the 82 cancer specimens, 81 (98.7%) showed higher or equal expressions of NF-kappaB activity when compared to the adjacent normal tissue. Fifty-five cases (67.1%) had higher levels of NF-kappaB activity in the cancerous tissue than in the adjacent normal tissue (p<0.005). With regard to tumor size, steroid receptors, stages, histological types, and node status, there were no statistically significant differences in NF-kappaB activity between cancerous tissues and adjacent normal tissues. However, significantly higher expressions of NF-kappaB activity were seen in those cases with positive HER2/neu oncoprotein, poorly differentiated histological grades, high nuclear pleomorphisms, and high mitotic counts (p<0.05). Positive HER-2/neu overexpression of oncoprotein had higher NF-kappaB activity (86%) than negative overexpression (60%) (p<0.05). It has been shown that the NF-kappaB activity increases in the HER-2/neu oncoprotein overexpression in human breast cancer.
Overexpression of HER-2/neu gene could induce NF-kappaB activity in human breast cancer cells, as has been confirmed in other research on cell lines.
本研究调查了核因子-κB(NF-κB)活性在HER-2/neu癌蛋白过表达的人类乳腺癌中的作用,以及其在取自台湾乳腺癌患者的不同组织学分级癌细胞表达中的作用。
从82名女性乳腺癌患者中采集标本。通过免疫组织化学检测HER-2/neu癌蛋白。采用电泳迁移率变动分析评估NF-κB活性表达,并在乳腺癌组织和相邻正常组织中使用抗P65抗体通过超迁移技术进行确认。组织学分级采用改良的布鲁姆-理查森分级方案进行测量。
在82个癌标本中,81个(98.7%)与相邻正常组织相比显示出更高或相等的NF-κB活性表达。55例(67.1%)癌组织中的NF-κB活性水平高于相邻正常组织(p<0.005)。关于肿瘤大小、类固醇受体、分期、组织学类型和淋巴结状态,癌组织和相邻正常组织之间的NF-κB活性无统计学显著差异。然而,在HER2/neu癌蛋白阳性、组织学分级差、核多形性高和有丝分裂计数高的病例中,NF-κB活性表达明显更高(p<0.05)。癌蛋白HER-2/neu过表达阳性的NF-κB活性(86%)高于过表达阴性(60%)(p<0.05)。已表明在人类乳腺癌中HER-2/neu癌蛋白过表达时NF-κB活性增加。
HER-2/neu基因的过表达可诱导人类乳腺癌细胞中的NF-κB活性,这已在其他细胞系研究中得到证实。