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Research ArticleExperimental Studies

Inhibition of Both Mesothelioma Cell Growth and Cdk4 Activity following Treatment with a TATp16INK4a Peptide

SANDRA P. FRIZELLE, MARIAN G. KRATZKE, RICHARD R. CARREON, SEAN C. ENGEL, LAURA YOUNGQUIST, MARK A. KLEIN, LAURA FOURRE, LAURIE L. SHEKELS and ROBERT A. KRATZKE
Anticancer Research January 2008, 28 (1A) 1-7;
SANDRA P. FRIZELLE
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MARIAN G. KRATZKE
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RICHARD R. CARREON
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SEAN C. ENGEL
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LAURA YOUNGQUIST
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MARK A. KLEIN
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LAURA FOURRE
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LAURIE L. SHEKELS
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ROBERT A. KRATZKE
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  • For correspondence: kratz003@umn.edu
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Abstract

Disruption of the 9p21 locus is common in mesothelioma and leads to loss of both the p16INK4a and the p14ARF gene products. This study tested the hypothesis that re-expression of p16INK4a carried out using the TAT delivery system that carries the protein transduction domain of the HIV TAT will result in mesothelioma cell death. Materials and Methods: A synthetic TATp16INK4a peptide and a charge matched control were transduced into mesothelioma cells in vitro and in vivo. Cells were assayed for Cdk4 inhibition, cell cycle arrest, and cell death. Results: Treatment of mesothelioma cells with TATp16INK4a for 48 hours resulted in cell death. Apoptosis and G1 cell cycle arrest was also observed. Following transduction of cells with TATp16INK4a there was complete but transient hypophosphorylation of pRb. Similar effects were observed in mesothelioma xenografts. Conclusion: Therapeutic strategies which introduce either TATp16INK4a peptide, or small molecule mimetic, could be an effective strategy for mesothelioma treatment.

  • Mesothelioma
  • p16INK4a
  • cyclin dependent kinase
  • Received October 4, 2007.
  • Accepted October 16, 2007.
  • Copyright© 2008 International Institute of Anticaner Research (Dr. John G. Delinassios), All rights reserved
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Anticancer Research: 28 (1A)
Anticancer Research
Vol. 28, Issue 1A
January-February 2008
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Inhibition of Both Mesothelioma Cell Growth and Cdk4 Activity following Treatment with a TATp16INK4a Peptide
SANDRA P. FRIZELLE, MARIAN G. KRATZKE, RICHARD R. CARREON, SEAN C. ENGEL, LAURA YOUNGQUIST, MARK A. KLEIN, LAURA FOURRE, LAURIE L. SHEKELS, ROBERT A. KRATZKE
Anticancer Research Jan 2008, 28 (1A) 1-7;

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Inhibition of Both Mesothelioma Cell Growth and Cdk4 Activity following Treatment with a TATp16INK4a Peptide
SANDRA P. FRIZELLE, MARIAN G. KRATZKE, RICHARD R. CARREON, SEAN C. ENGEL, LAURA YOUNGQUIST, MARK A. KLEIN, LAURA FOURRE, LAURIE L. SHEKELS, ROBERT A. KRATZKE
Anticancer Research Jan 2008, 28 (1A) 1-7;
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