Relation of overexpression of S phase kinase-associated protein 2 with reduced expression of p27 and PTEN in human gastric carcinoma.
OBJECTIVE
To investigate the significance of S phase kinase-associated protein 2 (Skp2) expression in human gastric carcinoma and the relation between expressions of Skp2, p27 and PTEN.


METHODS
Immunohistochemical analysis was performed on 138 gastric carcinoma specimens, their paired adjacent mucosa specimens, 102 paired lymphatic metastatic carcinoma tissue specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, 10 chronic superficial gastritis specimens and 5 normal gastric mucosa specimens for Skp2 expression and on 138 gastric carcinoma specimens for p27 and PTEN expression.


RESULTS
Skp2 labeling frequency was significantly higher in intestinal metaplasia (12.68+/-0.86) and adjacent mucosa (19.32+/-1.22) than in normal gastric mucosa (0.53+/-0.13) and chronic superficial gastritis (0.47+/-0.19) (P = 0.000); in dysplasia (16.74+/-0.82) than in intestinal metaplasia (P = 0.000); in gastric primary carcinoma (31.34+/-2.17) than in dysplasia and adjacent mucosa (P = 0.000); in metastasis gastric carcinoma in lymph nodes (39.76+/-2.00) than in primary gastric carcinoma (P = 0.037), respectively. Skp2 labeling frequency was positively associated with differentiation degree (rho = 0.315, P = 0.000), vessel invasion (rho = 0.303, P = 0.000) and lymph node metastasis (rho = 0.254, P = 0.000) of gastric cancer. Expression of Skp2 was negatively associated with p27 (rho = -0.451, P = 0.000) and PTEN (rho = -0.480, P = 0.000) expression in gastric carcinoma. p27 expression was positively associated with PTEN expression in gastric carcinoma (rho = 0.642, P = 0.000).


CONCLUSIONS
Skp2 overexpression may be involved in carcinogenesis and progression of human gastric carcinoma in vivo, possibly via p27 proteolysis. PTEN may regulate the expression of p27 by negatively regulating Skp2 expression.
Ma
Xiu-Mei
XM
Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China.
Liu
Ying
Y
Guo
Jian-Wen
JW
Liu
Jiang-Hui
JH
Zuo
Lian-Fu
LF
D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000502:physiology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D044786:S-Phase Kinase-Associated Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human