Expression of nitric oxide synthase in human gastric carcinoma and its relation to p53, PCNA.
OBJECTIVE
To investigate the expression of NOS in gastric carcinoma, and to explore the relationship between the expression of nitric oxide synthases (NOS) and p53, PCNA, pathological features and clinical staging of gastric cancer.


METHODS
The activity of NOS protein was investigated in 85 samples of human gastric carcinoma and 25 samples of normal gastric mucosal tissue by biochemical assay. We then examined the expression of NOS, p53, PCNA in 85 samples of human gastric cancer was examined by immunohistochemistry, and NOS mRNA expression in 85 gastric cancer tissue specimens by in situ hybridization.


RESULTS
Biochemical assay showed that the activity of NOS was significantly higher in gastric carcinoma than in normal gastric mucosal tissues (t = 0.4161, P<0.01). Immunohistochemistry revealed that endothelial nitric oxide synthase (eNOS) expressed in all samples of normal gastric mucosa, but only 6 cases of 85 gastric cancer specimens showed weak positive immunohistochemical reactions to eNOS (20%). Inducible nitric oxide synthase (iNOS) was expressed strongly in human gastric carcinoma (81.2%). In situ hybridization analysis showed that iNOS mRNA expression was significantly stronger than eNOS mRNA expression in gastric cancer tissue (chi(2) = 10.23, P<0.01). The expression of iNOS in gastric cancer was associated with differentiation, clinical stages or lymph node metastases (r = 0.3426, P<0.05). However, iNOS expression did not correlate with histological classifications and morphological types. The expression of iNOS was significantly correlated with p53 or PCNA expression (r = 0.3612, P<0.05). The expression of neuronal nitric oxide synthase (nNOS) was not examined by immunohistochemistry and in situ hybridization in gastric cancer specimens and normal gastric mucosa.


CONCLUSIONS
In human gastric cancer, there is an enhanced expression of iNOS, but not of eNOS. NOS promotes the proliferation of tumor cells and plays an important role in gastric cancer spread. Inactivation of antioncogene p53 and overexpression of iNOS might play a synergetic role in the process of carcinogenesis of human gastric carcinoma.
Wang
Yong-Zhong
YZ
Department of Pathology, the Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China. zjwyzh@163.com
Cao
You-Qing
YQ
Wu
Jian-Nong
JN
Chen
Miao
M
Cha
Xiao-Ying
XY
D000230:Adenocarcinoma / Q000503:physiopathology* / Q000556:secondary; D000328:Adult; D000368:Aged; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000473:pathology / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II