Breast Cancer Research and Treatment

, Volume 114, Issue 2, pp 203–209

Programmed Cell Death 4 inhibits breast cancer cell invasion by increasing Tissue Inhibitor of Metalloproteinases-2 expression

  • René Nieves-Alicea
  • Nancy H. Colburn
  • Ann-Marie Simeone
  • Ana M. Tari
Preclinical Study

DOI: 10.1007/s10549-008-9993-5

Cite this article as:
Nieves-Alicea, R., Colburn, N.H., Simeone, AM. et al. Breast Cancer Res Treat (2009) 114: 203. doi:10.1007/s10549-008-9993-5

Abstract

High levels of the cyclooxygenase-2 (COX-2) protein have been associated with invasion and metastasis of breast tumors. Both prostaglandin E2 (PGE2) and interleukin-8 (IL-8) have been shown to mediate the invasive activity of COX-2 in breast cancer cells. Here we expand these studies to determine how COX-2 uses PGE2 and IL-8 to induce breast cancer cell invasion. We demonstrated that PGE2 and IL-8 decreased the expression of the tumor suppressor protein Programmed Cell Death 4 (PDCD4). We hypothesized that suppression of PDCD4 expression is vital to the invasive activity of PGE2 and IL-8. In MCF-7 cells overexpressing PDCD4 (MCF-7/PDCD4), PGE2 and IL-8 failed to induce invasion, in contrast to the parental MCF-7 cells, thus indicating that PDCD4 blocks breast cancer cell invasion. MCF-7/PDCD4 cells produced higher levels of the Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) than the parental cells. Silencing TIMP-2 mRNA in MCF-7/PDCD4 cells reversed the anti-invasive effects of PDCD4, allowing PGE2 and IL-8 to induce the invasion of these cells. Here we report the novel findings that suppression of PDCD4 expression is vital for the invasive activity of COX-2 mediated by PGE2 and IL-8, and that PDCD4 increases TIMP-2 expression to inhibit breast cancer cell invasion.

Keywords

Breast cancer invasion Interleukin-8 Programmed Cell Death 4 Prostaglandin E2 Tissue Inhibitor of Metalloproteinase-2 

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • René Nieves-Alicea
    • 1
  • Nancy H. Colburn
    • 2
  • Ann-Marie Simeone
    • 1
  • Ana M. Tari
    • 1
  1. 1.Department of Experimental TherapeuticsThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Laboratory of Cancer PreventionNational Cancer InstituteFrederickUSA

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