Document Detail

Involvement of PI3K/PTEN/AKT/mTOR pathway in invasion and metastasis in hepatocellular carcinoma: Association with MMP-9.
MedLine Citation:
PMID:  19208038     Owner:  NLM     Status:  PubMed-not-MEDLINE    
AIM: To investigate the status of Phosphatidylinositol 3-kinase (PI3K)/PTEN/AKT/mammalian target of rapamycin (mTOR) pathway and its correlation with clinicopathological features and matrix metalloproteinase-2, -9 (MMP-2, 9) in human hepatocellular carcinoma (HCC).
METHODS: PTEN, Phosphorylated AKT (p-AKT), Phosphorylated mTOR (p-mTOR), MMP-2, MMP-9 and Ki-67 expression levels were evaluated by immunohistochemistry on tissue microarrays containing 200 HCCs with paired adjacent non-cancerous liver tissues. PTEN, MMP-2 and MMP-9 mRNA levels were determined by real-time RT-PCR in 36 HCCs. The relationships between PI3K/PTEN/AKT/mTOR pathway and clinicopathological factors and MMP-2, 9 were analyzed in HCC.
RESULTS: In HCC, PTEN loss and overexpression of p-AKT and p-mTOR were associated with tumor grade, intrahepatic metastasis, vascular invasion, TNM stage and high Ki-67 labeling index (P < 0.05). PTEN loss was correlated with p-AKT, p-mTOR and MMP-9 overexpression. Furthermore, PTEN and MMP-2, 9 mRNA levels were down-regulated and up-regulated in HCC compared with paired non-cancerous liver tissues, respectively (P < 0.01). PTEN, MMP-2 and MMP-9 mRNA levels were correlated with tumor stage and metastasis. There was an inverse correlation between PTEN and MMP-9 mRNA expression. However, PI3K/PTEN/AKT/mTOR pathway was not correlated with MMP-2.
CONCLUSIONS: PI3K/PTEN/AKT/mTOR pathway, which is activated in HCC, is involved in invasion and metastasis through up-regulating MMP-9 in HCC.
Jing-Song Chen; Qian Wang; Xin-Hui Fu; Xiao-Hui Huang; Xi-Lin Chen; Liang-Qi Cao; Lian-Zhou Chen; Hao-Xiang Tan; Wen Li; Jiong Bi; Long-Juan Zhang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hepatology research : the official journal of the Japan Society of Hepatology     Volume:  39     ISSN:  1386-6346     ISO Abbreviation:  Hepatol. Res.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-11     Completed Date:  2011-07-14     Revised Date:  2014-07-30    
Medline Journal Info:
Nlm Unique ID:  9711801     Medline TA:  Hepatol Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  177-86     Citation Subset:  -    
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