Up-regulation of PIK3CA promotes metastasis in gastric carcinoma.
OBJECTIVE
To explore expressions of PIK3CA in the progression of gastric cancer from primary to metastasis and its effects on activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway.


METHODS
mRNA and protein levels of PIK3CA were assessed, respectively, by real-time quantitative polymerase chain reaction and immunohistochemistry in specimens of normal gastric mucosa, primary foci and lymph node and distant metastasis of gastric cancer. Akt and phosphorylated Akt protein were also examined by Western blotting in these tissues, in order to analyze the effect of PIK3CA expression level changes on the activation of PI3K/Akt signaling pathway.


RESULTS
PIK3CA mRNA in lymph node metastasis were approximately 5 and 2 folds higher, respectively, than that in the corresponding normal gastric mucosa and primary gastric cancer tissues (P < 0.05), while no statistical significance was found compared with distant metastasis. Immunohistochemically, PIK3CA protein expression was discovered in 7 (35%) specimens of 20 primary foci vs 10 (67%) of 15 of lymph node metastasis or 11 (61%) of 18 of distant metastasis (35% vs 67%, P = 0.015; 35% vs 61%, P = 0.044). With the increased level of PIK3CA expression, the total Akt protein expression remained almost unchanged, but p-Akt protein was upregulated markedly.


CONCLUSIONS
Increased expression of PIK3CA is expected to be a promising indicator of metastasis in gastric cancer. Up-regulation of PIK3CA may promote the metastasis of gastric cancer through aberrant activation of PI3K/Akt signaling.
Institute of Cancer Research, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China. zxkstar@126.com
Ji-Fang
JF
Liu
Xin-Ke
XK
Zhou
Jin-Hui
JH
Chen
Gao
G
Yi
He-Ge
HG
Chen
Ming-Chen
MC
Ba
Sheng-Qu
SQ
Lin
Yan-Chao
YC
Qi
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000201:enzymology / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation; D055815:Young Adult
D012333:RNA, Messenger; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D051057:Proto-Oncogene Proteins c-akt