[Altered expression of PTEN gene and LOH of its epigenetic microsatellite in gastric carcinoma].
OBJECTIVE
To investigate the expression of PTEN and loss of heterozygosity (LOH) of its epigenetic microsatellite in gastric carcinoma and explore their roles in progression of gastric carcinoma.


METHODS
LOH of epigenetic microsatellites of PTEN (D10S541, D10S583 and D10S1687) in advanced gastric cancer was detected by PCR-SSCP. Expression of PTEN mRNA and protein in normal gastric mucosa and gastric cancer was evaluated by RT-PCR and SABC immunohistochemistry, respectively. The relationship between expression of PTEN mRNA and protein and lymph node metastasis or LOH of microsatellites was discussed.


RESULTS
LOH of D10S541, D10S583 and D10S1687 was found in 37.5% (21/56) of advanced gastric cancers. The positive rates of PTEN mRNA expression were 80.4% (45/56), 45.5% (5/11) and 32.1% (18/56) in normal mucosa, early and advanced gastric carcinomas, respectively, while 78.6% (44/56), 44.5% (5/11) and 28.6% (16/56) at the protein level. PTEN mRNA and protein were less frequently expressed in early and advanced gastric carcinomas than that in normal gastric mucosa (P < 0.05). There was positive correlation between PTEN mRNA expression and LOH of microsatellites in advanced gastric carcinomas. PTEN protein expression paralleled with its mRNA expression (P < 0.05). The expression of PTEN mRNA and protein was negatively correlated with lymph node metastasis of advanced gastric carcinomas (P < 0.05).


CONCLUSIONS
Down-regulated expression of PTEN gene is found in different stages of gastric carcinoma, and is closely correlated with LOH of its epigenetic microsatellites, which probably is its underlying molecular mechanisms. It suggests that altered PTEN gene contributes to tumorigenesis and progression of gastric carcinomas.
Li
Jin-yi
JY
Armed Police General Hospital, Beijing 100039, China.
Zheng
Hua-chuan
HC
Yang
Lin
L
Xu
Lei
L
Yang
Xue-Fei
XF
Gao
Hong
H
Zhang
Yin-chang
YC
Xin
Yan
Y
D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human