Nf-¦Êb On Metastasis Of Gastric Cancer Related Gene Regulation And Clinical Significance

Gastric cancer remains one of the most common cancer types in China and its incidence has gradually increased in recent years in many cities. The clinical outcome for gastric cancer patients remains poor, with a 5-year survival rate of only 20% in all stages, and a mere 40% of all patients respond to surgical intervention. The role of NF-kB in malignancies has been explored in relation to regulation of apoptosis, tumor progression, and responses to chemotherapy and ionizing radiation. But its role specifically in the process of metastasis, especially in the gastric cancer, has not been examined in detail.Tumor metastasis is a complex series process, including 3 key steps, such as tumor cell deviation, transfer and development. Among these, the most important step is tumor invasion and new vessels formation. Blockage any step of these, the tumor metastasis could be inhibited. In these years, Nuclear transcription factor kappa B, NF-kB was proved to play critical role in the control of tumor metastasis.Degradation of basement membrane and extracellular matrix structures are important features of the metastatic process of invasion and metastasis of gastric cancer. Human heparanase, an endoglycosidase, specifically involved in cleaving heparan sulfate, was cloned recently, and its characteristic functions related to the invasion and metastasis of cancer cells have been reported.Urokinase-type plasminogen activator (uPA) is an important enzyme of degradation of extracellular matrix. The uPA gene can enhance the degradation of extracellar matrix, making the invasion to deep tissue and vessel of tumor cell easy, so leading to distant metastasis. The uPA gene is an important marker of prediction tumor metastasis.Many studies demonstraste the invasion and metastasis of tumor dependence on the synergistic action of the proteins hydrolysis system. In gastric carcinoma tissues, the expression of uPA and MMP-9 has good correlation, and the hydrolysis in the progress of gastric cacinoma invasion is the result of cooperation of uPA and MMP-9. The production and activity of MMPs is an important aspect of the invasion and metastasis of tumor cells, and the over expression of MMPs has repeatly proved in tumor tissues.It was reported recently that heparanase expression is regulated by NF-kB in tumor cell lines, suggesting an important role for the NF-kB signal transduction pathway in the metastatic process. However, little information is available concerning NF-kB activation and controlling the expression of heparanase gene expression in gastric carcinoma, which is one of the most aggressive forms of cancer. But there's little information about the relationship about the NF-kB activation and the heparanase expression in gastric cancer. It was reported that NF-kB modulates the expression of extracellular matrix proteins such as MMP-9 in prostate cancer cell line. And the similar results, NF-kB modulates the expression of uPA,was also reported in gastric cancer. But there's little reports about the relationship among the MMP-9, UPA and the activation of NF-kB in gastric cancer.We speculate that three important genes, such as heparanase, MMP-9 and uPA, which for the degradation of basement membrane and extracellular matrix structures were modulated by NF-kB.We undertook the present study to determine whether NF-kB is constitutively activated in gastric carcinoma tissues, at the same time, to evaluate the correlation between NF-kB activity and clinicopathological features, and to examine whether heparanse, MMP-9 and uPA gene expression are regulated by NF-kB activation in gastric carcinoma.Stable transfection of a mutant IkBa. lacking Ser32 and Ser36 that was insensitive to IKK-mediated phosphorylation and degradation resulted in inhibition of NF-kB activity. After stable transfection of high, moderate and low differentiated gastric cancer cell line with PCDNA-IkB. plasmid, the regulation of gene expression of NF-kB downstream was studied. And the tumor cell invasion activity was studied at the same time with the Boyden chamber. In this pape...