Activation of NF-κB in Human Breast Cancer and its Role in Cell Proliferation and Progresssion

摘要

OBJECTIVE To investigate the expression of the nuclear transcription factor NF-κB, ER, HER2 and PCNA in breast cancers, and to study the relationship between activation of NF-κB and clinicopathologic parameters including the level of PCNA, ER, HER2, lymph node involvement, tumor size and histological grade (differentiation). METHODS Sixty cases of human breast cancer tissues and adjacent non-neoplastic breast tissues were examined for NF-κB, HER2 and ER, as well as PCNA by immunohistochemical methods. In addition the clinicopathologic parameters of the patients including lymph node involvement , tumor size and histological grade (differentiation) were collected. RESULTS The expression of NF-κB in the breast cancers and adjacent non -neoplastic breast tissue was 50.0% (30/60) and 40.0% (24/60) respectively, resulting in no significant difference (P > 0.05). NF-κB and HER2 expression was positively correlated whereas NF-κB and ER expression was negatively correlated. The NF-κB activation was 77.8% (14/ 18) in the breast cancers that were ER~-/HER2~+, a level significantly higher (P < 0.001) in comparison to the other groups of patients. The expression of NF-κB in the low-differentiated group (grade Ⅲ) was 57.1%, and in the moderate-differentiated group (grade Ⅱ) was 50.3%, both of which were higher than the 35.7% found in the high-differentiated group (grade Ⅰ). NF-κB activation in the cancers was significantly correlated with the histological grade (P < 0.05), PCNA expression (P=0.003) and lymph node involvement and tumor size (P=0.03 and 0.002, respectively). CONCLUSION NF -κB was activated abnormally in a portion of the breast cancers. The finding that NF-κB activation was positively correlated with HER2 expression, the level of PCNA, tumor grade,size and lymph node involvement is in accord with the ability of NF-κB to promote cellular proliferation and migration, clearly identifies the protein as a hallmark for targeted dysregulation in oncogenesis. NF-κB may be a hopeful target for breast cancer therapy.