Journal Article

Effect of γ-Linolenic Acid on the Transcriptional Activity of the Her-2/neu (erbB-2) Oncogene

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

in JNCI: Journal of the National Cancer Institute

Volume 97, issue 21, pages 1611-1615
Published in print November 2005 | ISSN: 0027-8874
Published online November 2005 | e-ISSN: 1460-2105 | DOI: http://dx.doi.org/10.1093/jnci/dji343

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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.

Journal Article.  4496 words.  Illustrated.

Subjects: Medical Oncology

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