Brief Article
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World J Gastroenterol. Oct 21, 2010; 16(39): 4986-4991
Published online Oct 21, 2010. doi: 10.3748/wjg.v16.i39.4986
Up-regulation of PIK3CA promotes metastasis in gastric carcinoma
Ji-Fang Liu, Xin-Ke Zhou, Jin-Hui Chen, Gao Yi, He-Ge Chen, Ming-Chen Ba, Sheng-Qu Lin, Yan-Chao Qi
Ji-Fang Liu, Xin-Ke Zhou, Gao Yi, Sheng-Qu Lin, Yan-Chao Qi, Institute of Cancer Research, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China
Jin-Hui Chen, Key Laboratory of Marine Bio-resources Sustainable Utilization, CAS, Guangzhou 510301, Guangdong Province, China
Jin-Hui Chen, Laboratory of Applied Marine Biology, Southern China Sea Institute of Oceanology, Chinese Academy of Science, Guangzhou 510301, Guangdong Province, China
He-Ge Chen, Department of Pharmacology and Experimental Therapeutics, University of Maryland, 685 West Baltimore street, Baltimore, MD 21228, United States
Ming-Chen Ba, Department of Abdominal Surgery (Section II), Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China
Author contributions: Liu JF and Zhou XK contributed equally to this work; Liu JF, Chen JH and Yi G performed the majority of experiments; Chen HG, Ba MC, Lin SQ and Qi YC offered new reagents and helpful comments during the study; Liu JF and Chen JH wrote and approved the paper.
Supported by Medical Research Fund of Guangdong Province, No. A2007284; and Health Bureau Fund of Guangzhou, No. 2009-YB-169
Correspondence to: Xin-Ke Zhou, Professor, Institute of Cancer Research, Affiliated Tumor Hospital of Guangzhou Medical College, Guangzhou 510095, Guangdong Province, China. zxkstar@126.com
Telephone: +86-20-83595208 Fax: +86-20-83489984
Received: June 7, 2010
Revised: July 13, 2010
Accepted: July 20, 2010
Published online: October 21, 2010
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: PIK3CA, Phosphatidylinositol 3-kinase/Akt pathway, Metastasis, Gastric cancer, Akt