Activation of Akt-mTOR-p70S6K pathway in angiogenesis in hepatocellular carcinoma.
Angiogenesis is an essential process for progression of hepatocellular carcinoma (HCC). The Akt-mTOR-p70S6K signal pathway has been recognized for its roles in regulating neoangiogenesis. The role of activation of the pathway in HCC progression is poorly understood. This study aimed to evaluate the immunohistochemical expression of the phosphorylated forms of the three key constituent proteins (Akt, mTOR and p70S6K) of the Akt-mTOR-p70S6K signal pathway in HCC and non-HCC tissue. Formalin-fixed paraffin-embedded tissue sections of 51 HCC, 9 hepatocellular adenoma (HCA), 48 cirrhotic nodules (CN) and 17 normal liver tissues (NLT) were immunostained for p-Akt, p-mTOR and p-p70S6K. The number of p-Akt and p-p70S6K-positive sinusoidal endothelial cells (SEC) and the intensity of immunostaining were significantly increased in HCC compared with HA, CN and NLT (p<0.01). p-mTOR in SEC tended to have an increased expression in SEC in HCC versus non-HCC tissue (p>0.05). There was a significant correlation between a high p-Akt and p-p70S6K expression, and a venous and capsular invasion of HCC. Our results suggest that activation of the Akt-mTOR-p70S6K pathway plays a significant role in HCC progression by promoting neoangiogenesis. Molecular strategies aimed at inhibiting this signal pathway may be of therapeutic use for the treatment of HCC.
Li
Wei
W
Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, TX 77030, USA. wei.li@uth.tmc.edu
Tan
Dongfeng
D
Zhang
Zhaoping
Z
Liang
John J
JJ
Brown
Robert E
RE
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000473:pathology; D042783:Endothelial Cells / Q000737:chemistry; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000032:analysis / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000032:analysis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases