[Constitutive activation and clinical significance of Stat3 in human gastric cancer tissues and cell lines].
OBJECTIVE
To investigate the activation of signal transducers and activators of transcription 3 (Stat3) in different types of gastric cancer cell lines and tissues and evaluate the relationship with their clinicopathological parameters.


METHODS
Western blotting and electrophoretic mobility shift assay (EMSA) were used to detected the expression of Stat3 protein and Stat3 DNA-binding activity in normal human gastric epithelial cell line 3T3 and five gastric cancer cell lines with different differentiation: MKN28, SGC7901, MKN45, AGS and NCI-SNU-1, respectively. The localization of phospho-Stat3 was determined by immunocytochemistry. The expressive intensity of phospho-Stat3 protein in 50 cases of gastric cancer tissues and adjacent normal mucosa were measured by immunohistochemistry.


RESULTS
Compared with normal gastric epithelial cell line 3T3, elevated activities of Stat3 were found in five different human gastric cancer cell lines. The Stat3 DNA-binding activity in moderately and poorly differentiated stomach adenocarcinoma cell lines (SGC7901, MKN45 and AGS) was higher than that of other cell lines (MKN28 and NCI-SNU-1). Phospho-Stat3 was detected primarily in the nuclei of AGS cells. The expressive intensity of phospho-Stat3 protein was significantly increased in gastric cancer tissues as compared with the adjacent normal gastric mucosa, especially in moderately and poorly differentiated cancers (both P < 0.05). The expressive intensity of phospho-Stat3 protein in stage II and stage III tumors was higher than that in stage I tumors (P < 0.05). No statistic difference of phospho-Stat3 expression was found between stage IV and stage I tumors (P > 0.05). The expression of phospho-Stat3 was closely correlated with the differentiation of gastric cancer.


CONCLUSIONS
Elevated activity of Stat3 can be found in different types of human gastric cancer cell lines and gastric cancer. JAK/STAT signal transduction pathway may play an important role in the development of human gastric cancer.
Yu
Li-fen
LF
Department of Gastroenterology, Ruijin Hospital of Shanghai Second Medical University, Shanghai 200025, China.
Zhu
Yan-bo
YB
Qiao
Min-min
MM
Zhong
Jie
J
Tu
Shui-ping
SP
Wu
Yun-lin
YL
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011496:Protein Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D011484:Protein-Arginine N-Methyltransferases; D050796:STAT3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases