乳腺癌细胞核因子κB活化及其在增殖与演化过程中的作用

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目的探讨NF-κB、雌激素受体(ER)、人上皮细胞生长因子受体-2(HER2)和增殖细胞核抗原(PCNA)等在乳腺癌中的蛋白表达特征,以及NF-κB活化与乳腺癌的ER、HER2、PCNA表达水平以及肿瘤淋巴结转移、肿瘤大小和组织学分级等临床病理学指标之间的相关性。方法采用免疫组化方法对60例乳腺癌和对应的癌旁组织的NF-κB、ER、HER2和PCNA等分子标志物的表达情况进行检测分析,同时收集对应的临床病理学数据。结果60例乳腺癌和癌旁组织的NF-κB活化率分别为50.0%(30/60)和40.0%(24/60)。乳腺癌与对应的癌旁组织的NF-κB活化率差异无显著性(P>0.05)。乳腺癌组织中的NF-κB活化与HER2表达呈正相关,与ER表达呈负相关。ER阴性/HER2阳性组的乳腺癌组织的NF-κB活化率为77.8%(14/18),明显高于其他组(P<0.001)。组织学分化低级别的乳腺癌组织的NF-κB活化率分别为57.1%(Ⅲ级)和50.3%(Ⅱ级),明显高于高分化组35.7%(Ⅰ级)(P<0.05)。乳腺癌组织的NF-κB活化率也与其大小和淋巴结转移相关,同时也与乳腺癌细胞的PCNA表达水平相关。结论乳腺癌的演化过程中有不同程度的NF-κB活化,但与HER2表达呈正相关,与ER表达呈负相关。NF-κB具有促进增殖和迁移、抑制分化和凋亡的作用,是乳腺癌形成过程中的一个发生失调的分子,可能成为抗癌治疗的靶位。 Objective To investigate the protein expression characteristics of NF-κB, estrogen receptor (ER), human epithelial growth factor receptor-2 (HER2) and proliferating cell nuclear antigen (PCNA) in breast cancer, and the activation of NF-κB and mammary glands. The correlation between the ER, HER2, and PCNA expression levels of the cancer and the clinicopathological parameters such as tumor lymph node metastasis, tumor size, and histological grade. Methods Immunohistochemistry was used to detect the expression of NF-κB, ER, HER2, PCNA and other molecular markers in 60 cases of breast cancer and corresponding adjacent tissues, and corresponding clinical pathological data were collected. Results The activation rates of NF-κB in 60 cases of breast cancer and adjacent tissues were 50.0% (30/60) and 40.0% (24/60), respectively. There was no significant difference in the activation rate of NF-κB between breast cancer and its corresponding adjacent tissue (P>0.05). NF-κB activation in breast cancer tissues was positively correlated with HER2 expression and negatively correlated with ER expression. The activation rate of NF-κB in breast cancer tissues with ER-negative/HER2-positive group was 77.8% (14/18), which was significantly higher than that in other groups (P<0.001). The activation rate of NF-κB in histologically differentiated low-grade breast cancer tissues was 57.1% (level III) and 50.3% (level II), respectively, which was significantly higher than that of high-differentiation group (35.7%, level I) (P<0.05). The activation rate of NF-κB in breast cancer tissues is also related to its size and lymph node metastasis, and it is also related to the PCNA expression level of breast cancer cells. Conclusion There are different degrees of NF-κB activation during the evolution of breast cancer, but there is a positive correlation with HER2 expression and a negative correlation with ER expression. NF-κB has the functions of promoting proliferation and migration, inhibiting differentiation and apoptosis, and is an imbalanced molecule in the process of breast cancer formation, and may become a target of anti-cancer therapy.
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