[Decreased expression of Cx32 and Cx43 and their function of gap junction intercellular communication in gastric cancer].
OBJECTIVE
The aim of this study was to investigate the expression of connexin (Cx) and the function of gap junction intercellular communication (GJIC) in the carcinogenesis, progression and metastasis of gastric cancers.


METHODS
Immunohistochemistry was used to detect the expression of Cx32 and Cx43 proteins in tissue samples. Indirect immunofluorescence assay was used to investigate the expression of Cx32 and Cx43 proteins in several gastric cancer lines of various differentiation grades. The expression of Cx43 in samples of gastric cancer tissue, adjacent normal tissue and in the gastric cancer cell lines of various differentiation grades was detected by Western blot. Scrape-loading dye transfer (SLDT) technique was used to detect the function of gap junction intercellular communication (GJIC) in the various cell lines.


RESULTS
In the normal gastric mucosa the expression rates of both Cx32 and Cx43 were 100%. In gastric cancers, the expression rates of Cx32 andCx43 were 49.5% (55/111) and 39.6% (44/111), respectively. There was a significant difference between their expression in normal and cancer tissues (P < 0.05). Age of the patients was not significantly correlated with the expression level of Cx32 and Cx43 (P > 0.05). Cx43 expression was significantly associated with the TMN stage, histological type, depth of infiltration and distant metastasis (P < 0.05), but Cx32 expression was not significantly correlated with depth of infiltration ( P > 0.05). In the cancer cell lines, a positive expression of Cx32 and Cx43 was detected in transfected human stomach mucosal cell line (CES-1) and human well differentiated stomach cancer cell line (N87), but negative in the poorly differentiated stomach cancer cell line (BGC-823) at all. Both Cx32 and Cx43 expression rates were 100% in the cell line GES-1. Cx32 expression rate was 49.0% and Cx43 expression rate was 55.0% in the cell line N87. But in the poorly differentiated cancer cell line BGC-823 both Cx32 and Cx43 expression was negative. GJIC function detection showed: GES-1 showed well GIJC function but no GIJC function in the cell lines N87 and BGC-823. The intensity of fluorescence was gradually decreasing from GES-1 cells to N87 cells and almost no fluorescence in BGC-823 cells. Western blotting showed that Cx43 expression in normal tissue was higher than that in gastric cancer tissue, and in the cell lines GES-1, N87 and BGC-823, the bands seemed decreasing progressively. There was very low expression in BGC-823 cells.


CONCLUSIONS
The decreasing expression of connexin Cx32 and Cx43 is obviously correlated with the occurrence, development and metastatic potential of stomach cancers.
Wu
Jin
J
The Seventh Medical Department, Tumor Hospital of Harbin Medical University, Harbin 150040, China.
Zhou
Hong-Feng
HF
Wang
Cui-Hua
CH
Zhang
Bo
B
Liu
Dan
D
Wang
Wen
W
Sui
Guang-Jie
GJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D000097002:Gap Junction beta-1 Protein
D018031:Connexin 43; D017630:Connexins; D000097002:Gap Junction beta-1 Protein