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Related Experiment Videos

PTEN controls tumor-induced angiogenesis.

S Wen1, J Stolarov, M P Myers

  • 1Section of Hematology/Oncology, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Department of Biochemistry and Molecular Biology, Indiana School of Medicine, Indianapolis, IN 46202, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 29, 2001
PubMed
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The tumor suppressor PTEN (phosphatase and tensin homolog) inhibits brain tumor progression by suppressing angiogenesis, the formation of new blood vessels. Restoring PTEN function reduces tumor growth and improves survival in mice.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Mutations in the PTEN (phosphatase and tensin homolog) tumor suppressor gene are linked to the progression of brain tumors.
  • Tumor progression, especially in malignant forms, involves angiogenesis, a process known as the angiogenic switch.

Purpose of the Study:

  • To investigate whether PTEN regulates brain tumor progression by modulating angiogenesis.
  • To determine the role of PTEN's lipid phosphatase activity in the angiogenic response.

Main Methods:

  • U87MG glioma cells with reconstituted PTEN (wild-type and a mutant) were used in an orthotopic nude mouse brain tumor model.
  • Tumor growth, survival, AKT phosphorylation, thrombospondin 1 expression, and angiogenic activity were assessed.

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Main Results:

  • Reconstitution of wild-type PTEN significantly decreased tumor growth in vivo and prolonged survival without affecting in vitro proliferation.
  • PTEN reconstitution reduced AKT phosphorylation, induced thrombospondin 1 expression, and suppressed angiogenic activity.
  • These effects were dependent on PTEN's lipid phosphatase activity, as the inactive G129E mutant did not elicit similar responses.

Conclusions:

  • PTEN regulates tumor-induced angiogenesis and glioma progression to malignancy.
  • PTEN's lipid phosphatase activity is crucial for controlling the angiogenic response in vivo.
  • PTEN acts via phosphoinositide-dependent signals to inhibit glioma progression.