Growth, invasion, metastasis, differentiation, angiogenesis and apoptosis of gastric cancer regulated by expression of PTEN encoding products.
OBJECTIVE
To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.


METHODS
Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113 cases of gastric cancers were studied for the expression of PTEN and Caspase-3 and microvessel density (MVD) by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.


RESULTS
Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9 % vs 89.4 %; P=0.000, chi(2)=33.474). PTEN expression was significantly associated with invasive depth (P=0.003, rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren's classification (P=0.000, rs=0.345), and histological classification (P=0.005, rs=0.262) of tumors, but not with tumor size (P=0.639, rs=0.045), Borrmann's classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020, F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 % vs 50.4 %; P=0.007, chi(2)=7.286). Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, chi(2)=15.266).


CONCLUSIONS
Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth, differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3 to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.
Zheng
Hua-Chuan
HC
Lab. 4, Cancer Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. zheng_huachuan@hotmail.com
Li
Yi-Ling
YL
Sun
Jin-Min
JM
Yang
Xue-Fei
XF
Li
Xiao-Han
XH
Jiang
Wei-Guo
WG
Zhang
Yin-Chang
YC
Xin
Yan
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology / Q000556:secondary; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases