| Esophageal cancer is one kinds of malignant tumor,the most common pathological histology is squamous cell cancer.About 300,000 people died because of esophageal cancer each year all over the world,China is a high incidence area of esophageal cancer in the world,the morbidity and mortality of esophageal cancer are both high.Researches show that the occurrence and development of esophageal cancer is a complex process with interactions of many factors,multi-stage and poly genes,and there are also many abnormal activation of singnaling pathways.Therefore,clarify the mechanism of esophageal cancer by studying the singnaling pathways in the development of esophageal cancer,is still the goal of esophageal cancer treatment research.Many researches confirmed that mTOR/P70S6 K signaling transduct--ion pathway was over activation in the development of multiple tumors.mTOR pathway is considered to be the main signal regulation pathway of protein synthesis,involved in cell proliferation,differentiation,migra tion,etc.It actives phosphorylation P70S6 K which can promote mRNA translation and produce a variety of proteins for the cell cycle across G1 period.Reports showed that mTOR was expressed in breast cancer,colon cancer and lymphoma,but there were few reports in esophageal cancer.In this study,we explore the expressions of mTOR and p-P70S6 K in esophageal cancer by immunohistochemistry,Western Blot and RT-PCR technology,analyze their relationship with other clinical pathological features,and observe the effects of mTOR/P70S6 K signaling pathway in the development of esophageal cancer.It will provide new ideas for the clinical treatment of esophageal cancer.Objective:To investigate the effects of mTOR/P70S6 K signalingpathway in the development of esophageal cancer and the related mechanisms.Methods:1 The expressions of mTOR and p-P70S6 K in 90 cases of esophageal cancer were detected by using immunohistochemistry(sp method).All the cases were divided into different groups according to degree of age,gender,invasive depth,differentiation and clinical staging.After getting the positive rate of two molecules in each groups,we analyzed the relationship between two molecules and clinical pathological features,and futher explored the essential role between the two molecules and esophageal cancer biological behavior.2 Total proteins were extracted from 30 cases of fresh carcinoma tissues and adjacent mucosa,each groups were divided by different clinical staging.The expressions of mTOR and p-P70S6 K were detected by using Western Blot.We analyzed their relationship with esophageal cancer clinical staging.3 Total RNAs were extracted from 30 cases of fresh carcinoma tissues and adjacent mucosa,each groups were divided by different degree of differentiation.The expression of mTOR and P70S6 K were detected by using RT-PCR and the results were shown as relative quantity.We investigated their relationship with esophageal cancer differentiation.Results:1 Immunohistochemical results:(1)The expression of mTOR in esophageal squamous cancer tissues and adjacent mucosaThe positive rate of mTOR in carcinoma tissues was 70.00%(63/90),and adjacent mucosa was 15.00%(3/20).The expression of mTOR was significantly higher in carcinoma tissues than that in adjacent mucosa,the difference was statistically significant(P<0.05).(2)The relationship between mTOR and clinical pathological featuresThe expression of mTOR protein was related with esophageal cancer differentiation,invasive depth and clinical staging.The positive rate of mTOR in low-grade esophageal cancer was48.72%(19/39),and high-grade esophageal cancer was 86.27%(44/51);the positive rate of mTOR in esophageal cancer in mucous layer was 11.11%(1/9),in muscle layer was 55.88%(19/34),and in fibrous membranes was91.49%(43/47),the positive rate was gradually increased;the positive rate of mTOR in Ⅰ-Ⅱ stage esophageal cancer was 52.78%(19/36),and in Ⅲ-Ⅳstage was 81.48%(44/54),the differences were all statistically significant(P<0.05).mTOR was not related with age,gender,lymph node metastasis and vascular tumor embolus,there was no significant difference(P>0.05).(3)The expression of p-P70S6 K in esophageal squamous cancer tissues and adjacent mucosaThe positive rate of p-P70S6 K in carcinoma tissues was 71.11%(64/90),and adjacent mucosa was 5.00%(1/20).The expression of mTOR was significantly higher in carcinoma tissues than that in adjacent mucosa,the difference was statistically significant(P<0.05).(4)The relationship between p-P70S6 K and clinical pathological featuresThe expression of p-P70S6 K protein was related with esophageal cancer differentiation,invasive depth and clinical staging.The positive rate of p-P70S6 K in low-grade esophageal cancer was56.41%(22/39),and high-grade esophageal cancer was 82.35%(42/51);the positive rate of p-P70S6 K in esophageal cancer in mucous layer was22.22%(2/9),in muscle layer was 70.59%(24/34),and in fibrous membranes was 80.85%(38/47);the positive rate of p-P70S6 K in Ⅰ-Ⅱ stage esophageal cancer was 50.00%(18/36),and in Ⅲ-Ⅳ stage was 85.19%(46/54),the differences were all statistically significant(P<0.05).p-P70S6 K was not related with age,gender,lymph node metastasis and vascular tumor embolus,there was no significant difference(P>0.05).(5)There is a positive correlation between the expression of mTOR and p-P70S6 K in esophageal squamous cancer tissues(rp= 0.492,P =0.000).2 Western Blot results:Western Blot results showed the expression of mTOR and p-P70S6 K inadjacent mucosa and esophageal squamous cancer tissues which was divided into Ⅰ-Ⅱ stage and Ⅲ-Ⅳ stage esophageal cancer according to clinical staging.(1)The expression of mTOR protein was gradually increased(0.440±0.023,0.712±0.021,0.836±0.018)in each groups,the difference was statistically significant(P<0.05).(2)The expression of p-P70S6 K protein was gradually increased(0.237±0.011,0.454±0.022,0.620±0.042)in each groups,the difference was statistically significant(P<0.05).3 RT-PCR results:RT-PCR results showed the expression of mTOR and p-P70S6 K in adjacent mucosa and esophageal squamous cancer tissues which was divided into low-grade and high-grade esophageal cancer according to degree of differentiation.(1)The expression of m TOR m RNA was gradually increased(0.484±0.030,0.715±0.018,0.912±0.015)in each groups,the difference was statistically significant(P<0.05).(2)The expression of p-P70S6 K m RNA was gradually increased(0.288±0.202,0.643±0.028,0.814±0.189)in each groups,the difference was statistically significant(P<0.05).Conclusions: The expressions of mTOR and p-p70S6 K in esophageal squamous cell carcinoma are much higher than in adjacent mucosa.Moreover,they are related with esophageal cancer differentiation,invasive depth and clinical staging.It suggestes that mTOR/P70S6 K signaling pathway is connected with the occurrence and development of esophageal squamous cancer.This study provides a new idea for early diagnosis and treatment of esophageal cancer. |
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