+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and -independent mechanisms in HepG2 cells

PTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and -independent mechanisms in HepG2 cells

Carcinogenesis 31(7): 1211-1219

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor, and increased levels of vascular endothelial growth factor (VEGF) are associated with progression of HCC. Tumor suppression gene PTEN (phosphatase and tensin homolog deleted on chromosome 10), an important antagonist of the phosphoinositide-3-kinase (PI3K)/adenosine triphosphate-dependent tyrosine kinase (Akt) pathway, is also commonly lost or mutated in HCC. However, the effect of PTEN on VEGF-mediated angiogenesis in HCC remains unknown. To explore this relationship, we expressed a panel of PTEN mutants in human HCC cells with low expression of PTEN (HepG2 cells). Overexpression of PTEN in HepG2 cells resulted in the downregulation of proliferation and migration of cocultured endothelial cells and decreased expression of hypoxia-inducible factor 1 (HIF-1) and VEGF. Similarly, using a nude mouse model, we demonstrated that PTEN decreased expression of HIF-1 and VEGF and suppressed HepG2-induced angiogenesis. This inhibitory effect was not observed in cells expressing a phosphatase-deficient PTEN mutant, suggesting that PTEN inhibits angiogenesis and VEGF through a phosphatase-dependent pathway. Strikingly, reintroducing the C2 domain of PTEN also resulted in a significant decrease in angiogenesis and VEGF expression, although it did not affect Akt phosphorylation or HIF-1 expression. In summary, this study suggests the novel viewpoint that PTEN suppresses angiogenesis and VEGF expression in HCC through both phosphatase-dependent and -independent mechanisms.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 054842333

Download citation: RISBibTeXText

PMID: 20430845

DOI: 10.1093/carcin/bgq085

Related references

PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. Proceedings of the American Association for Cancer Research Annual Meeting 44: 1368, July, 2003

Connexin26 regulates the expression of angiogenesis-related genes in human breast tumor cells by both GJIC-dependent and -independent mechanisms. Cell Communication & Adhesion 10(4-6): 387-393, 2003

PTEN regulates angiogenesis through PI3K/Akt/VEGF signaling pathway in human pancreatic cancer cells. Molecular and Cellular Biochemistry 331(1-2): 161-171, 2010

Kaempferol inhibits angiogenesis and VEGF expression through both HIF dependent and independent pathways in human ovarian cancer cells. Nutrition and Cancer 61(4): 554-563, 2009

PTEN induces apoptosis and up-regulates p53 expression in HepG2 cells. Zhonghua Gan Zang Bing Za Zhi 12(12): 745-748, 2004

Retinoic acid represses CYP7A1 expression in human hepatocytes and HepG2 cells by FXR/RXR-dependent and independent mechanisms. Journal of Lipid Research 51(8): 2265-2274, 2010

VEGF-C differentially regulates VEGF-A expression in ocular and cancer cells; promotes angiogenesis via RhoA mediated pathway. Angiogenesis 14(3): 371-380, 2011

Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines. Human Molecular Genetics 19(22): 4319-4329, 2011

Hedgehog regulates distinct vascular patterning events through VEGF-dependent and -independent mechanisms. Blood 116(4): 653-660, 2010

Activation of Toll-like receptor 7 regulates the expression of IFN-λ1, p53, PTEN, VEGF, TIMP-1 and MMP-9 in pancreatic cancer cells. Molecular Medicine Reports 13(2): 1807-1812, 2016

The DEK oncogene activates VEGF expression and promotes tumor angiogenesis and growth in HIF-1α-dependent and -independent manners. Oncotarget 7(17): 23740-23756, 2016

Cryptotanshinone down-regulates the expression of VEGF and inhibits angiogenesis in U2OS osteosarcoma cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 32(1): 29-33, 2016

Butyrate-induced phosphatase regulates VEGF and angiogenesis via Sp1. Archives of Biochemistry and Biophysics 478(1): 85-95, 2008

MT1-MMP up-regulates VEGF expression in human breast carcinoma MCF-7 cells and induces tumor angiogenesis. Zhonghua Zhong Liu Za Zhi 31(10): 727-731, 2011