Constitutive activation of Stat3 signaling pathway in human colorectal carcinoma.
OBJECTIVE
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-x(L) 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-x(L) 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-x(L) 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).


CONCLUSIONS
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.
Ma
Xiang-Tao
XT
Department of Surgery, Peking University People's Hospital, Beijing 100044, China.
Wang
Shan
S
Ye
Ying-Jiang
YJ
Du
Ru-Yu
RY
Cui
Zhi-Rong
ZR
Somsouk
Ma
M
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators