Targeting Breast Cancers Featuring Activating Mutations in PIK3CA by Generating a Lethal Dose of PIP3

Abstract

The level of PIP3 is tightly regulated by the activities of two opposing enzymes, phosphatidylinositol 3-kinase (PI3K) and Phosphatase and tensin homolog (PTEN), acting as "on/off" switches. We hypothesized that PI3K activity is tolerated within a relatively narrow window in cells - "too much of PIP3 is just as lethal as too little", thus PIK3CA/PTEN double mutants may elevate PIP3 to a lethal level. To test this hypothesis, we determined the effect of PTEN inactivation in human mammary epithelial cells carrying activated alleles of PIK3CA. We also generated a Tet-regulated transgenic mouse mammary tumor model expressing oncogenic PIK3CA and produced mammary tumor induced by mammary gland specific loss of PTEN. We are now ready to test our hypothesis in vivo with concurrent activation of PIK3CA and inactivation of PTEN.

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Document Details

Document Type
Technical Report
Publication Date
Feb 01, 2009
Accession Number
ADA506562

Entities

People

  • Jean J. Zhao

Organizations

  • Dana–Farber Cancer Institute

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Culture Techniques
  • Department Of Defense
  • Epithelial Cells
  • Genes
  • Glands
  • Lethal Dosage
  • Mammary Glands
  • Mutations
  • Neoplasms

Readers

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  • Molecular Biology and Genetics