Mechanisms of Growth Factor Attenuation of Cell Death in Chemotherapy Treated Breast Cancer Cells

Abstract

The purpose of this research project was study the mechanisms for insulin-like growth factor-I (IGF-I) mediated survival responses in breast cancer cells treated with chemotherapy or radiation. To this end, we have focused on the survival kinase, Akt and also the kinase which conveys cell death messages induced by chemotherapy or radiation treatment, JNK (c-Jun N-terminal kinase). Interestingly, IGF-I treatment of breast cancer cells induces the activity of both kinases Akt and JNK. Our recent work with Akt confirm that its activity protects cells form chemotherapy. The MCF-7 breast cancer cell line that we use for our studies is protected from ICF-I activation of Akt but not through pathways that have been described thus far. In fact, these cells are resistant to the cell death pathway that is typically activated with chemotherapy and radiation treatment. Therefore, we are currently studying new mechanisms for Akt mediated cell survival. Our work to identify how JNK conveys cell death signals in response to UV or chemotherapy treatment indicates that JNK can also down-regulates growth factor mediated signaling. Inhibition of JNK, in the absence of chemotherapy or radiation, also causes cell cycle arrest and inhibits breast cancer cell proliferation.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2003
Accession Number
ADA424046

Entities

People

  • Carla Van Den Berg

Organizations

  • University of Colorado Health

Tags

DTIC Thesaurus Topics

  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Chemotherapy
  • Growth Factors
  • Health Services
  • Neoplasms
  • Peptide Growth Factors
  • Peptides
  • Programmed Cell Death
  • Proteins

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology (Cancer Research).