Effect of γ-linolenic acid on the transcriptional activity of the Her-2/neu (erbB-2) oncogene

Javier A. Menendez, Luciano Vellon, Ramon Colomer, Ruth Lupu

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Abstract

The ω-6 polyunsaturated fatty acid γ-linolenic acid (GLA; 18:3n-6), which is found in several plant oils and is used as an herbal medicine, has antitumor activity in vitro. We examined the effect of GLA on the expression of the Her-2/neu (erbB-2) oncogene, which is involved in development of numerous types of human cancer. Flow cytometric and immunoblotting analyses demonstrated that GLA treatment substantially reduced Her-2/neu protein levels in the Her-2/neu-overexpressing cell lines BT-474, SK-Br3, and MDA-MB-453 (breast cancer), SK-OV3 (ovarian cancer), and NCI-N87 (gastrointestinal tumor derived). GLA exposure led to a dramatic decrease in Her-2/neu promoter activity and a concomitant increase in the levels of polyomavirus enhancer activator 3 (PEA3), a transcriptional repressor of Her-2/neu, in these cell lines. In transient transfection experiments, a Her-2/neu promoter bearing a PEA3 site-mutated sequence was not subject to negative regulation by GLA in Her-2/neu-overexpressing cell lines. Concurrent treatments of Her-2/neu-overexpressing cancer cells with GLA and the anti-Her-2/neu antibody trastuzumab led to synergistic increases in apoptosis and reduced growth and colony formation.

Original languageEnglish (US)
Pages (from-to)1611-1615
Number of pages5
JournalJournal of the National Cancer Institute
Volume97
Issue number21
DOIs
StatePublished - Nov 2 2005

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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