The Contribution of P27Kip1 Regulation to Tamoxifen Resistance

Abstract

In the course of this project, I investigated the role of the cell cycle inhibitor P27 in response to antiestrogens and TGF-beta. Using ER positive MCF-7 lines, this work revealed 27 is an essential mediator of 61 arrest by antiestrogens. In resistant cell lines P27 deregulation was found to occur via increased MAPK activation. Inhibition of MAPK signaling restored antiestrogen sensitivity. P27 is not only an essential mediator of antiestrogens, but also plays a role in 61 arrest by TGF-beta. P27 was an essential mediator of 61 arrest in malignant breast cancer lines, but not in normal finite lifespan mammary epithelial cells. Compensation by P21 and P130 allowed maintenance of 61 arrest despite forced P27 deregulation.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2002
Accession Number
ADA407216

Entities

People

  • Jeffrey C. Donovan
  • Joyce M Slingerland

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Colon Cancer
  • Cultured Cells
  • Epithelial Cells
  • Genetics
  • Neoplasms
  • Oncology
  • Peptide Growth Factors
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Medicine

Readers

  • Breast cancer cell signaling and growth regulation.
  • Molecular Biology and Genetics