The clinical significance between activation of nuclear factor kappa B transcription factor and overexpression of HER-2/neu oncoprotein in Taiwanese patients with breast cancer

Background: 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. Materials and methods: 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. Results: 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. Conclusion: 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. (C) 2003 Elsevier Science B.V. All rights reserved.