Control of Metastatic Colonization in Prostate Cancer: The Functional Mechanism of Metastasis Suppression by JNKK1/MKK4

Abstract

The purpose of the award was to provide Dr. Szmulewitz with training in basic and translational prostate cancer (PC) research. The scientific focus is PC metastasis modeling and modulation of metastatic colonization (the specific outgrowth of microscopic disseminated cancer cells to overt macroscopic metastases) through the prostate cancer metastasis suppressor JNKK1/MKK4. In addition the scope of the award also includes key training opportunities. Over the second year of this award Dr. Szmulewitz continues to utilize resources within the cancer community at the University of Chicago. He continues to take coursework critical to his career development as a physician-scientist and is now an integrated member of the University of Chicago Comprehensive Cancer Center. Dr. Szmulewitz has completed the work to date outlined within the Statement of Work. The scientific aim of the award was to show that the metastasis suppressor JNKK1/MKK4 when ectopically expressed in Dunning PC cells, impairs metastatic colonization through alteration in proliferation at the secondary site where the kinase is activated. Studies have been completed and analyzed within Aim 1 supporting that JNKK1/MKK4 mediated metastasis suppression is imparted through a transient delay in cell-cycle progression. Furthermore, studies within Aim 2 have shown that this transient delay in metastasis formation is a delay in proliferation within the first 14 days post dissemination. Eventual outgrowth of metastases is concordant with a loss in JNKK1/MKK4 kinase activity within the overt metastases, signifying an initial activation of the kinase, leading to suppression of colonization after dissemination, and eventual cellular adaptation through loss of kinase activity. This work was recently published in The International Journal of Cancer.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2011
Accession Number
ADA554126

Entities

People

  • Russell Szmulewitz

Organizations

  • University of Chicago

Tags

DTIC Thesaurus Topics

  • Biostatistics
  • Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Data Analysis
  • Data Science
  • Department Of Defense
  • Diseases And Disorders
  • Information Science
  • Medical Personnel
  • Neoplasms
  • Oncology
  • Ovarian Cancer
  • Prostate Cancer
  • Regression Analysis
  • Standards

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  • Clinical Trial Research.
  • Molecular Biology and Genetics