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 oncogen
To determine the regulatory effects of estrogen and cytokine IL-6 and IL-8 on the growth of epithelial ovarian cancer （OVCA）, we first examined the status of estrogen receptors （ERα and ERβ）, IL-6 receptor （IL-6Rα and gp130）, and IL-8 receptor （IL-8RA and IL-8RB） on five epithelial OVCA cell lines by semiquantitative RT-PCR and Western blot analysis. Results showed that the expressions of these receptors were variable on the five cells. Those OVCA ceUs expressing the receptors were selected to study related molecular mechanism. MTT assay was performed to observe the effects of 17β-estradiol （E2）, IL-6 and IL-8 on cell proliferation. We discovered that E2 markedly promoted the proliferation of CAOV-3 and OVCAR-3 cell in a time- and dose-dependent manner. Tamoxifen （Txf）, an ER inhibitor, completely blocked the proliferation of the E2-induced cells, and IL-6- or/and IL-8-neutralizing antibody only showed partially blocking activity. IL-6 and IL-8 were able to significantly stimulate CAOV-3 and OVCAR-3 cell proliferation in a time- and dose-dependent manner, which had a potential synergistic effect on CAOV-3 cells but not on OVCAR-3 cells. The cell proliferation induced by these two cytokines was abolished completely by their specific neutralizing antibodies, partially by Txf, but not by unrelated goat IgG. Taken together, our results suggested that estrogen, IL-6 and IL-8 could modulate OVCA growth by forming a reciprocal cascade with amplifying effect.
Yue WangJie YangYan GaoYongrui DuLeyuan BaoWenyan NiuZhi Yao
