The Expression Of Rac1 Protein In Gastric Cancer And Its Role In Gastric Cancer Metastasis By S-P Method

The incidence of gastric cancer is at the top of digestive tumor, which takes about 170,000 lives. It is at the top of all types of tumors in our country .The incidence of Gastric cancer in our country is high,and its prevalence rate was about ten thousand 30.1/10 per year. Its death rate is also at the top of all the malignant tumor,which accounted for near 1 / 4 of almost all malignant tumor .There are more than 20,000 patients who are nearly found suffered with gastric cancer every year ,It is indeed a disease of gastric cancer such as gastric wall infiltration depth, the degree of credit organizations, lymph node metastasis ( particular in the invasion and metastasis) play an important role,in the development prognosis and outcome of gastric cancer.Also its affection on gastric cancer is through hout the whole clinical course and particularly invasive growth and the distant metastasis is the direct cause which influence prognosis of gastric cancer. It has been proved that Rac1 has a closely recationship with the tumor invasion and metastasis by a mount of studies. The expression of Rac1 is apparently increased in some malignant tumor, while it has no or low lever expression .in the corresponding normal tissues,and its expression level level is closely related to the invasion and metastasis capacily of tumor cell.Rac1-wide was known as the Ras-related C3 botulinum toxin substrate 1, which is a class of important intracellular signaling molecule, in cell signal transduction pathway play the role of signal converter or molecular switch,Racl has two forms which are GTP binding from(active status)and GDP binding form(inactive status), Racl will have signal transcluction activity when combining with GTP and it can combine with effected moleculer of downstream(such as PAK etc).Racl will lose signal transduction activity when it departs from GTP and in the state of combinding with GDP.They can be converted between each other. It is the process of GDP phosphorylaction ,that is from the form of GDP combination to the form of GTP combination and the opposite is the process of GTP phosphorylaction.Resting state, Rac1 and GDP binding, and Rho-GDIs form a complex remain in the cytoplasm. When the signal to stimulate the acceptance, Rac1 release from Rho-GDIs down, and on location at the cell membrane, when in the GEF (such as Tiam1) the effect of, GTP to replace GDP, Rac1 activation . Cytokine-induced STAT tyrosine phosphorylation and activation of STAT translocation into the nucleus to activate target genes. STAT nuclear translocation when, Rac1 and its GTPase activating protein with the combination of the first RacGAP become complex. Phosphorylation of STAT3 and STAT5A formed complexes are necessary in order to complete the transposition . Therefore, activation of Rac1 into the nucleus together with the STAT. To sum up the state of Rac1 inactivation may be located in cytoplasm, in the activation of Rac1 may be located in the cell membrane or nucleus. In order to understand the expression of Rac1 protein conformation and the two forms of orientation in the cell, and then explore the Racl activation in the occurrence of gastric cancer and the role of the transfer mechanism for the application of clinical laboratory to carry out gastric tumor genetic markers to detect and evaluation of benign and malignant tumors lay the theoretical foundation for the transfer.In this study, using the immunohistochemical S-P method to detect the enzyme-based positioning and expression of Racl protein in gastric cancer cells, and further using IPP method to test the immunohistochemical semi-quantitative of Racl protein and analyze experimental results statistically.The results showed that①S-P method Rac1-positive rate of expression: in gastric cancer tissue than benign lesions were 84.6%(44/52) >16.7%(2/12) (P<0.01); metastasis of gastric cancer than those without metastasis were 94.7%(36/38)>57.1%(8/14),(P<0.01).②IPP method to the average optical density (x±s) that semi-quantitative Rac1: gastric cancer group was higher than that in GBD group were0.22±0.11>0.02±0.05,(P<0.01): gastric cancer metastasis group were higher than those without metastasis to 0.26±0.08> 0.11±0.10 (P<0.01).③Rac1 protein enzyme histochemical color type only have a slurry-type and mixed type , karyotype appears. Slurry-type gastric cancer which accounted for 19.2%(10/52). Accounted for 65.4%(34/52) hybrid; GBD in slurry-type accounts for only 16.7%(2/12).④In the 52 cases of gastric carcinoma mixed activated Rac1 protein expression positive rate: the poorly differentiated group was higher than that of high, medium differentiation group were 76.5% (26/34) >44.4% (8/18); T3 ~ T4 group was higher than T1 ~ T2 were 75.0% (27/36) >43.7% (7/16); lymph node metastasis group was higher than that without metastasis were 78.9% (30/38) > 28.6% (4/14); Clinical III-IV group was higher than I-II were 77.8%(28/36)>37.5%(6/16),mixed type Rac1 protein With the expression of the degree of differentiation of gastric carcinoma with reduced depth of deeper invasion, clinical stage increased and the incidence of lymph node metastasis have a higher trend.The Conclusion is that the positive rate of Racl protein expression and semi-quantitative in gastric cancer tissue was significantly higher than that of benign pathological changes tissue, reflecting Rac1 in gastric cancer is related to the role. The positive rate of Racl protein expression and semi-quantitative metastasis in gastric cancer is higher than those tissue without metastasis, reflecting the promotion role of Rac1 in the transfer of tumor.The first time in using immunohistochemical SP method Rac1 in gastric cancer in two conformational forms of enzyme-based positioning color. Proved to the reflecting in activation state of Rac1 protein exists in the cell membrane and nucleus of gastric cancer were mixed, reflecting in inactivation state of Rac1 protein exists in the cytoplasm of gastric cancer was slurry-type, Rac1 protein in the form of two types of conformation, the Rac1 protein in activation is related with the gastric cancer metastasis closely and plays a promotional role in the transfer mechanism of tumor and furthermore related with the invasion depth, differentiation degree and clinical stage of gastric cancer.