Pim-1: A Molecular Target to Modulate Cellular Resistance to Therapy in Prostate Cancer

Abstract

The contract supports studies to define the role of the PIM1 kinase in acquired resistance to chemotherapy by prostate cancer cells. Data to date for specific aim #1 define a signaling pathway induced by docetaxel, involving sequential steps of STAT3 activation, expression of PIM1, and activation of NFkB signaling. Blockade of this pathway by expression of dominant negative PIM1proteins blocks drug-induced upregulation of NFkB activity, and sensitizes cells to docetaxel. Other studies (specific aim #2) focus on identifying a mechanism through which PIM1 activates NFkB. We have unambiguously identified S937 as the major PIM1 phosphorylation site on the NFKB1/p105 precursor protein, through use of LCM/MS/MS analysis. Interestingly PIM2 is only a weak kinase for this site. Additional data (specific aim #3) have been generated to characterize a small molecule inhibitor of PIM1.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2005
Accession Number
ADA453390

Entities

People

  • Michael Lilly

Organizations

  • Loma Linda University

Tags

DTIC Thesaurus Topics

  • Cell Physiological Processes
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Health Services
  • Hematologic Diseases
  • Lymphatic Diseases
  • Medical Personnel
  • Myeloid Cells
  • Neoplasms
  • Peptides
  • Prostate Cancer
  • Small Molecules
  • Therapy

Fields of Study

  • Chemistry
  • Medicine

Readers

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