Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma

被引:100
作者
Ma, Xiang-Tao [1 ]
Wang, Shan [1 ]
Ye, Ying-Jiang [1 ]
Du, Ru-Yu [1 ]
Cui, Zhi-Rong [2 ]
Somsouk, Ma [3 ]
机构
[1] Peking Univ, Peoples Hosp, Dept Surg, Beijing 100044, Peoples R China
[2] Peking Univ, Peoples Hosp, Div Surg Oncol, Beijing 100044, Peoples R China
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Dept Med, Boston, MA 02114 USA
基金
中国国家自然科学基金;
关键词
D O I
10.3748/wjg.v10.i11.1569
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AIM: Signal transducers and activators of transcription (STATs) are a family of transcription factors activated in response to cytokines and growth factors. Constitutive activation of Stat3 has been observed in a growing number of tumor-derived cell lines, as well as tumor specimens from human cancers. The purpose of this study was to investigate the expression of p-Stat3, activated form of Stat3, and its downstream mediators including cyclin D1 and Bcl-xL in colorectal carcinoma (CRC), and to explore the possible mechanism of Stat3 signaling pathway in the tumorigenesis of colorectal carcinoma. METHODS: Tissue samples from 45 patients of primary colorectal carcinoma were selected for studying Stat3 signaling pathway protein expression. Western blot analysis was used to measure the expression of p-Stat3, cyclin D1, and Bcl-xL proteins in colorectal carcinomas. Furthermore, the expression patterns of these proteins were analyzed for their distribution at the cellular level by immunohistochemical staining of the tissues. RESULTS: Protein levels of p-Stat3, cyclin D1, and Bcl-xL were increased in colorectal carcinomas compared with adjacent normal mucosae (P<0.05). Elevated levels of p-Stat3 were correlated with the nodal metastasis and the stage (P<0.05). Overexpression of cyclin D1 was associated with the nodal metastasis (P<0.05). There was also a significant correlation between the expressions of p-Stat3 and cyclin D1 (r=0.382, P<0.05). CONCLUSION: Constitutive activation of Stat3 may play an important role in the tumorigenesis of colorectal carcinoma, and the detailed mechanism of Stat3 signaling pathway in CRC deserves further investigation.
引用
收藏
页码:1569 / 1573
页数:5
相关论文
共 37 条
  • [1] c-Myb and Bcl-x overexpression predicts poor prognosis in colorectal cancer -: Clinical and experimental findings
    Biroccio, A
    Benassi, B
    D'Agnano, I
    D'Angelo, C
    Buglioni, S
    Mottolese, M
    Ricciotti, A
    Citro, G
    Cosimelli, M
    Ramsay, RG
    Calabretta, B
    Zupi, G
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (04) : 1289 - 1299
  • [2] Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis
    Bowman, T
    Broome, MA
    Sinibaldi, D
    Wharton, W
    Pledger, WJ
    Sedivy, JM
    Irby, R
    Yeatman, T
    Courtneidge, SA
    Jove, R
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (13) : 7319 - 7324
  • [3] STATs in oncogenesis
    Bowman, T
    Garcia, R
    Turkson, J
    Jove, R
    [J]. ONCOGENE, 2000, 19 (21) : 2474 - 2488
  • [4] Stat proteins and oncogenesis
    Bromberg, J
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (09) : 1139 - 1142
  • [5] Stat3 as an oncogene
    Bromberg, JF
    Wrzeszczynska, MH
    Devgan, G
    Zhao, YX
    Pestell, RG
    Albanese, C
    Darnell, JE
    [J]. CELL, 1999, 98 (03) : 295 - 303
  • [6] Stat3 activation is required for cellular transformation by v-src
    Bromberg, JF
    Horvath, CM
    Besser, D
    Lathem, WW
    Darnell, JE
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (05) : 2553 - 2558
  • [7] Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma
    Campbell, CL
    Jiang, Z
    Savarese, DMF
    Savarese, TM
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (01) : 25 - 32
  • [8] Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells
    Catlett-Falcone, R
    Landowski, TH
    Oshiro, MM
    Turkson, J
    Levitzki, A
    Savino, R
    Ciliberto, G
    Moscinski, L
    Fernández-Luna, JL
    Nuñez, G
    Dalton, WS
    Jove, R
    [J]. IMMUNITY, 1999, 10 (01) : 105 - 115
  • [9] STATs and gene regulation
    Darnell, JE
    [J]. SCIENCE, 1997, 277 (5332) : 1630 - 1635
  • [10] Stat3 activation in prostatic carcinomas
    Dhir, R
    Ni, ZY
    Lou, W
    DeMiguel, F
    Grandis, JR
    Gao, AC
    [J]. PROSTATE, 2002, 51 (04) : 241 - 246