摘要
背景与目的:转录信号转导子与激活子3(signal transducers and activatorsof transcription 3,Stat3)通路受细胞因子与生长因子的刺激而活化,参与调节细胞的增殖、分化与凋亡。Stat3因可以介导细胞的恶性转化而被确认为是癌基因。本研究分析Stat3及其靶基因产物cyclin D1与Bcl-x_L在结直肠癌组织与细胞中的表达情况,探讨Stat3及其靶基因产物在结直肠癌发病机制中的作用。方法:用Western blot检测45例结直肠癌组织、癌旁肠粘膜以及结肠癌细胞系SW480和HCT116中Stat3(p-stat3)及其靶基因产物cyclin D1和Bcl一x_L蛋白表达,用免疫组织化学染色进行细 胞内定位,同时对结直肠癌组织中p-Stat3、cyclin D1及Bcl-x_L表达情况与不同临床病理特征进行统计学分析。结果:结直肠癌组织中p-Stat3、cyclin D1及Bcl-x_L蛋白表达率分别为57.8％、64.4％及68.9％,癌旁肠粘膜表达率分别为42.2％、35.6％及31.1％;其蛋白表达水平(A值)分别为114263±53 598、58 321±24 872、71 032±43 425;癌旁肠粘膜分别为55 971±28 762、22 563±11 160、37 281±14 622(P<0.05)。p-Stat3表达水平与结直肠癌临床分期及淋巴结转移有关(P=0.026,0.018),cyclin D1与淋巴结转移有关(P=0.041)。p-Stat3与cyclin D1在结直肠癌组织中表达情况呈?
BACKGROUND & OBJECTIVE: Signal transducers and activators of transcription 3 (Stat3) pathway can be activated by cytokines and growth factors, and activation of Stat3 is involved in modulating cell proliferation, differentiation, and apoptosis. Stat3 has been classified as an oncogene because Stat3 can mediate malignant transformation of cultured cells. This study was conducted to investigate the expression of Stat3 and its target gene products including Cyclin D1 and Bcl-xL in human colorectal carcinoma (CRC) tissues and cells, and to explore the mechanisms in tumorigenesis of CRC. METHODS: The expression of Stat3, p-Stat3, Cyclin D1, and BCl-XL in 45 cases of cancerous tissues, adjacent normal tissues, and two colon cancer cell lines including SW480 and HCT116 was measured by Western blot analysis. The expression pattern of Stat3 and its activated form p-Stat3 was determined by immunohistochemical staining. The relationship of the expression of p-Stat3, Cyclin D1, and BC|-XL in CRC with various clinicopathological characteristics was analyzed statistically. RESULTS: The protein expression rates of p-Stat3, Cyclin D1, and Bcl-xL in colorectal cancer and adjacent normal mucosa were 57. 8%, 64.4%, 68.9%, and 42. 2%, 35.6%, 31.1%, respectively; and their protein levels (lvalue) were 114263±53598, 58321±24872, 71032±43425 in colorectal cancer and 55971±28762, 22563±11160, 37281±14622 in adjacent normal mucosa (P <0.05). Overexpression of p-Stat3 was correlated with clinical stage and nodal metastasis in colorectal cancer (P = 0.026 and P= 0.018, respectively). Elevated levels of Cyclin D1 were associated with nodal metastasis ( P= 0. 041) . It was found that Cyclin D1 was in a positive linear correlation fashion with p-Stat3 in tumor ( r = 0. 382, P <0. 05). Activated Stat3 was also detected in both colon cancer cell lines SW480 and HCT116. CONCLUSION: Stat3 signaling pathway may play an important role in the tumorigenesis of colorectal carcinoma. Determination of Stat3 and its target gene products can be used to indicate the malignancy degree of colorectal carcinoma.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2003年第11期1135-1139,共5页
Chinese Journal of Cancer
基金
国家自然科学基金(No.30271269)
