Novel Therapeutic Approaches Toward Treating Prostate Cancer

Abstract

The Pim protein kinase is over expressed in prostate cancer. To clarify the role of this protein in regulating normal prostate and cancer growth we have investigated its mechanism of action. We demonstrate that inhibition of AKT in prostate cancer cell lines induces the expression of multiple receptor tyrosine kinases (RTKs), but increases the protein levels of serine threonine protein kinase Pim-1. Pim-1 activity is identified as essential in the feedback regulation of RTK levels by AKT inhibition. Pim-1 appears to control RTKs by regulating the translation of these proteins in a cap-independent mechanism. Both tissue culture and animal experiments demonstrate that the combination of AKT and Pim inhibitors provide synergistic inhibition of tumor growth. Thus, this combination therapy has the potential activity to be developed as a prostate cancer treatment.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 2012
Accession Number
ADA589866

Entities

People

  • Andrew S Kraft

Organizations

  • Medical University of South Carolina

Tags

DTIC Thesaurus Topics

  • Biological Sciences
  • Blood
  • Cell Line
  • Cells
  • Chemical Synthesis
  • Chemistry
  • Combination Therapy
  • Epithelial Cells
  • Health Services
  • Myeloid Cells
  • Neoplasms
  • Neutral Amino Acids
  • Prostate Cancer
  • Small Molecules
  • Stem Cells
  • Therapy
  • Tissues

Fields of Study

  • Biology

Readers

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  • Molecular and genetic basis of cancer.