Activation of PI3K/PKB Signaling in Breast Cancer May Inhibit TGF-Beta-Induced G1 Arrest Through Changes in p27 Function

Abstract

Loss of responsiveness to TGF-beta-induced cell cycle inhibition is a hallmark of cancers and the underlying mechanisms are not well understood. We now show PKB activation contributes to resistance to antiproliferative signals including TGF-beta and breast cancer progression in part by impairing nuclear import and action of p27. We observed in TGF-beta resistant human mammary epithelial cells, PKB is overactivated and p27 is mislocalized in the cytoplasm and the nuclear localization of p27 can be restored by PI3K inhibition. PKB transfection caused cytoplasmic p27 accumulation and resistance to cytokine-mediated G1 arrest.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2002
Accession Number
ADA412221

Entities

People

  • Jiyong Liang
  • Joyce M Slingerland

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Diseases And Disorders
  • Epithelial Cells
  • Growth Factors
  • Health Services
  • Medical Personnel
  • Neoplasms
  • Peptide Growth Factors
  • Peptides
  • Proteins
  • Transcription Factors
  • Tumor Cell Line

Readers

  • Molecular Biology and Genetics