Invasive and angiogenic phenotype of MCF-7 human breast tumor cells expressing human cyclooxygenase-2

Jenifer R. Prosperi, Susan R. Mallery, Kristina A. Kigerl, Abigail A. Erfurt, Fredika M. Robertson

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

To evaluate the direct effect of human cyclooxygenase-2 (hCox-2) on human breast tumor cell proliferation, invasion, and angiogenesis, hCox-2 cDNA was transfected into slow growing, non-metastatic MCF-7 human breast tumor cells that express low levels of Cox-2. Two stable transfectant clones, designated MCF-7/hCox-2 clones 8 and 10, had significantly decreased (P<0.05) doubling time, with two-fold greater number of cells during exponential growth compared to the MCF-7/vector control. Proliferation of both of the MCF-7/hCox-2 clones was significantly inhibited in a time- and dose-dependent manner by celecoxib. The MCF-7/hCox-2 clones 8 and 10 formed larger and greater numbers of colonies in soft agar than the MCF-7/vector control, with a corresponding increased invasion across an artificial Matrigel basement membrane in response to recombinant human epidermal growth factor (hEGF). The MCF-7/hCox-2 clones 8 and 10 had higher mRNA levels of two splice variants of vascular endothelial growth factor (VEGF), V145 and V165. These results demonstrate that hCox-2 directly increases breast tumor cell proliferation, stimulates invasion across a basement membrane, and induces synthesis of specific heparin binding splice variants of VEGF.

Original languageEnglish (US)
Pages (from-to)249-264
Number of pages16
JournalProstaglandins and Other Lipid Mediators
Volume73
Issue number3-4
DOIs
StatePublished - Apr 1 2004

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Keywords

  • Human epidermal growth factor
  • MMLV-RT
  • MMP-2
  • MT-MMP-1
  • Matrix metalloproteinase-2
  • Membrane type matrix metalloproteinase 1
  • Moloney murine leukemia virus reverse transcriptase
  • PCR
  • Polymerase chain reaction
  • VEGF
  • Vascular endothelial growth factor
  • hEGF

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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