5-Lipoxygenase regulates malignant mesothelial cell survival: Involvement of vascular endothelial growth factor

Mario Romano, Alfonso Catalano, Michele Nutini, Etrusca D'Urbano, Carlo Crescenzi, Joan Claria, Roberta Libner, Giovanni Davi, Antonio Procopio

Research output: Contribution to journalArticle

Abstract

Evidence indicates that lipoxygenases (LO) may play a role in cancer cell survival. We show that human malignant pleural mesothelial (MM) cells, but not normal mesothelial (NM) cells, express a catalytically active 5-LO. Pharmacological or genetic inhibition of MM cell 5-LO determined nucleosome formation and induced a DNA fragmentation pattern typical of apoptosis. This was completely reversed by exogenously added 5(S)-HETE but not by 12(S)-, 15(S)-HETE, or leukotriene (LT)B4. A 5-LO antisense oligonucleotide potently and time-dependently reduced vascular endothelial growth factor (VEGF) mRNA and constitutive VEGF accumulation in the conditioned media of MM cells. When NM cells were transfected with a 5-LO cDNA, basal and arachidonic acid-induced VEGF formation increased consistently by 6- and 12-fold, respectively. This was associated with a significant increase in DNA synthesis that was counteracted by a specific anti-VEGF antibody. Arachidonic acid and 5(S)-HETE also potently stimulated the activity of a VEGF promoter construct. Thus, 5-LO is a key regulator of MM cell proliferation and survival via a VEGF-related circuit.

Original languageEnglish
Pages (from-to)2326-2336
Number of pages11
JournalFASEB Journal
Volume15
Issue number13
DOIs
Publication statusPublished - 2001

Keywords

  • Angiogenesis
  • Apoptosis
  • Arachidonic acid
  • Eicosanoids
  • Mesothelioma

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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  • Cite this

    Romano, M., Catalano, A., Nutini, M., D'Urbano, E., Crescenzi, C., Claria, J., Libner, R., Davi, G., & Procopio, A. (2001). 5-Lipoxygenase regulates malignant mesothelial cell survival: Involvement of vascular endothelial growth factor. FASEB Journal, 15(13), 2326-2336. https://doi.org/10.1096/fj.01-0150com