Nuclear Factor-κB P65 (RelA) Transctription Factor Is Activated In Human Cardiac Carcinoma Tissue

Purpose: Activation of transcription factor nuclear factor kappa B(NF-κB) has been proved to play an important role in cell proliferation, apoptosis, cytokine production, and the activation of oncogenesis. Protein p65 is one of major constitutive integrants. The purpose of this research was to determine whether NF-κB is over-activated in human cardiac carcinoma tissues, and to determine the correlation between NF-κB activition and clinicopathological features of cardiac carcinoma. And then, we want to determine the correlations with VEGF and MMP-9 which were two kinds of invasion-related factors. We studied them to determine the relation of NF-κB and the aggressive process of cardiac carcinoma.Experimental Design: The specimens came from the operations of 39 cardiac carcinoma patients. They were identified to two groups. One group, including 34 carcinoma tissues and 10 stumps, was to determine NF-κB activation by formalin-fixed, paraffin-embedded specimens for immunohistochemical analysis. And, the other group, including 39 carcinoma tissues and 9 stumps, was fixed by70% alcohol in 4。C for FCM (flow cytometry) analysis. We used nuclear staining of RelA as a marker of NF-κB activation. The expressions of MMP-9 and VEGF were determined with RelA/p65 simultaneously.Results: Immunohistochemical analysis: The rate of activation of RelA in tumor tissues was significantly higher than the rate in stumps (P=0.031). Protein p65 was correlated to the depth of invasion (P=0.042) and TNM stages (P=0.023). VEGF, an angiogenesis-related factor, was proved higher expression in human cardiac tumor tissue (P=0.006). And, its higher expression was correlated to tumor lymph node metastases (P＜0.05) and TNM stages (P＜0.01). MMP-9, as an invasion-related factor, was also higher expression in human cardiac tumor tissues than in stumps (P＜0.01). Its higher expression was correlated with tumor lymph node metastases (P＜0.05), tumor grading (P＜0.01) and TNM stages (P＜0.05). There was significant correlation between p65 and VEGF expression. But there was not the same significant correlation between p65 and MMP-9 expression. Flow cytometry (FCM) analysis: The activation of RelA in tumor tissues was significantly higher than that in stumps (P＜0.01). Protein p65 was correlated to tumor lymph node metastases (P＜0.01) and its TNM pathological stages (P＜0.01). VEGF was found higher expression in human cardiac tumor tissue (P＜0.01). Its higher expression was correlated to the depth of invasion (P＜0.01) and lymphnode metastases (P＜0.05). MMP-9 was also higher expression in human cardiac tumor tissues (P＜0.01). Its higher expression was correlated with the depth of invasion (P＜0.05), tumor lymph node metastases (P＜0.01) and TNM stages(P＜0.01). There was significant correlation between p65 and MMP-9 expression(P＜0.05). But there was not the same significant correlation between it and VEGF expression.Conclusions: 1. The data showed that NF-κB had been constitutively activated in human cardiac carcinoma tissues. The data showed that the activation of NF-κB was related to the depth of invasion, lymph node metastases and the TNM stages. The later TNM stages, deeper invasion and lymph node metastases were correlated with the activation of NF-κB, which proved that the activation of NF-κB played an important role in the initiation and growth of cardiac cacinoma. 2. The expression of VEGF was higer in cardiac cacinoma tissues than in stumps tissues. Later TNM stages, deeper invasion and lymph node metastases were correlated with the expression of VEGF. 3. The expression of MMP-9 was higer in cardiac cacinoma tissues than in stumps tissues.later TNM stages, deeper invasion, lower tumor grading and lymph node metastases were correlated with the expression of MMP-9. 4. The expression of MMP-9 or the expression of VEGF had relation to the activation of NF-κB. VEGF and MMP-9 might be the taget gene of NF-κB.