The Role of p90rsk in Breast Cancer Cell Survival from Apoptosis

Abstract

Evidence suggests that sensitivity to chemotherapy is largely due to a functional apoptotic pathway. Thus, a better understanding of the signal transduction pathways that lead to rescue from apoptosis might lead to improved modalities of treatment for unresponsive cancer types. The focus of this proposal was to elucidate the role of p9Orsk in antagonizing apoptosis in breast cancer cells. P9Orsk is a serine-threonine protein kinase in the Ras-Raf-ERK (extracellular signal-regulated kinase, also known as mitogen- activated protein kinase or MAP kinase) cascade that lies immediately downstream of ERK. Although the Ras pathway and ERKs have been the focus of much research in the cancer field, less is known about the role of p9Orsk. We hypothesize that p9Orsk may be particularly relevant to breast cancer cell survival because evidence suggests it can not only directly phosphorylate and activate the estrogen receptor but also has the potential to antagonize apoptosis through neutralizing BAD, a proapoptotic member of he Bcl family of proteins. In addition, new evidence suggests to its activation by PDKl (3-phosphatidyl inositol 3, 4, 5 phosphate dependent protein kinase) in addition to ERKl/2 activation. We proposed to study p9Orsk since it may provide a new target in breast cancer therapy.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2003
Accession Number
ADA425646

Entities

People

  • Lucy Y. Ghoda

Organizations

  • University of Colorado Health

Tags

DTIC Thesaurus Topics

  • Apoptosis
  • Biomedical Research
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Estrogens
  • Kinases
  • Neoplasms
  • Neutral Amino Acids
  • Phosphorylation
  • Proteins
  • Substrates
  • Survival
  • Threonine
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Cellular and Molecular Pathways of Apoptosis.
  • Oncology