[信号转导和转录激活因子3（Stat3）及其靶基因产物与人类结直肠癌恶性肿瘤的关系]

[Relationship of Stat3 and its target gene products with malignancy in human colorectal carcinoma].

作者信息

Ma Xiang-Tao, Wang Shan, Ye Ying-Jiang, Du Ru-Yu, Cui Zhi-Rong

机构信息

Department of Surgery, Division of Surgical Oncology, People's Hospital, Peking University, Beijing, PR China.

出版信息

Ai Zheng. 2003 Nov;22(11):1135-9.

PMID:14613639

Abstract

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-x(L) 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-x(L) 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 Bcl-x(L) in CRC with various clinicopathological characteristics was analyzed statistically.

RESULTS

The protein expression rates of p-Stat3, Cyclin D1, and Bcl-x(L) 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 (A value) 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.

摘要

背景与目的

信号转导及转录激活因子3（Stat3）通路可被细胞因子和生长因子激活，Stat3的激活参与调节细胞增殖、分化和凋亡。由于Stat3可介导培养细胞的恶性转化，因此已被归类为一种癌基因。本研究旨在探讨Stat3及其靶基因产物（包括细胞周期蛋白D1和Bcl-x(L)）在人大肠癌（CRC）组织和细胞中的表达情况，并探索CRC肿瘤发生的机制。

方法

采用蛋白质免疫印迹分析检测45例癌组织、癌旁正常组织以及两种结肠癌细胞系（SW480和HCT116）中Stat3、p-Stat3、细胞周期蛋白D1和Bcl-x(L)的表达。通过免疫组织化学染色确定Stat3及其激活形式p-Stat3的表达模式。对CRC中p-Stat3、细胞周期蛋白D1和Bcl-x(L)的表达与各种临床病理特征的关系进行统计学分析。

结果

p-Stat3、细胞周期蛋白D1和Bcl-x(L)在结直肠癌组织和癌旁正常黏膜中的蛋白表达率分别为57.8%、64.4%、68.9%和42.2%、35.6%、31.1%；其蛋白水平（A值）在结直肠癌中分别为114263±53598、58321±24872、71032±43425，在癌旁正常黏膜中分别为55971±28762、22563±11160、37281±14622（P<0.05）。p-Stat3的过表达与结直肠癌的临床分期和淋巴结转移相关（分别为P = 0.026和P = 0.018）。细胞周期蛋白D1水平升高与淋巴结转移有关（P = 0.041）。发现肿瘤中细胞周期蛋白D1与p-Stat3呈正线性相关（r = 0.382，P<0.05）。在结肠癌细胞系SW480和HCT116中也检测到激活的Stat3。