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Effect of dietary GLA+/−tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts

  1. Frances S. Kenny1,
  2. Julia M.W. Gee3,
  3. Robert I. Nicholson3,
  4. Ian O. Ellis2,
  5. Teresa M. Morris4,
  6. Susan A. Watson4,
  7. Richard P. Bryce5,
  8. John F.R. Robertson1,†,*

Article first published online: 2 MAR 2001

DOI: 10.1002/ijc.1213

Issue

International Journal of Cancer

International Journal of Cancer

Volume 92, Issue 3, pages 342–347, 1 May 2001

Additional Information

How to Cite

Kenny, F. S., Gee, J. M.W., Nicholson, R. I., Ellis, I. O., Morris, T. M., Watson, S. A., Bryce, R. P. and Robertson, J. F.R. (2001), Effect of dietary GLA+/−tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts. Int. J. Cancer, 92: 342–347. doi: 10.1002/ijc.1213

Author Information

  1. 1

    Professorial Unit of Surgery, City Hospital, Nottingham, United Kingdom

  2. 2

    Department of Histopathology, City Hospital, Nottingham, United Kingdom

  3. 3

    Tenovus Cancer Research Centre, University of Wales College of Medicine, Cardiff, United Kingdom

  4. 4

    Cancer Studies Unit, Department of Surgery, Queen's Medical Centre, Nottingham, United Kingdom

  5. 5

    Scotia Pharmaceuticals, Stirling, United Kingdom

  1. †

    Fax: +44-115-8402-618

*Professorial Unit of Surgery, City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK

Publication History

  1. Issue published online: 30 MAR 2001
  2. Article first published online: 2 MAR 2001
  3. Manuscript Accepted: 20 NOV 2000
  4. Manuscript Revised: 3 NOV 2000
  5. Manuscript Received: 22 MAY 2000

Funded by

  • Scotia Pharmaceuticals
  • Tenovus Organization
  • Departments of Surgery and Histopathology, Nottingham City Hospital, UK.

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Keywords:

  • gamma linolenic acid;
  • tamoxifen;
  • oestrogen receptor;
  • endocrine response;
  • breast cancer

Abstract

Gamma linolenic acid (GLA) possesses a number of selective anti-tumour properties including modulation of steroid receptor structure and function. We have investigated the effect of dietary GLA on the growth, oestrogen receptor (ER) expression and fatty acid profile of ER+ve human breast cancer xenografts. Experimental diets A, B, C, D were commenced after subcutaneous implantation of 40 female nude mice with the MCF-7 B1M cell line (Group A = control diet: B = control diet + GLA supplement: C = control diet + tamoxifen: D = control diet + GLA + tamoxifen; 10 mice/group). The mice were terminated when tumour cross-sectional area reached 250 mm2. ER H-scores were assessed by immunohistochemical assay and fatty acid profiles by gas-liquid chromatography of termination tumour samples. Groups C and D displayed significantly slower tumour growth (p =.0002, p =.0006) with trend for slower growth in B (p =.065) compared to control Group A. ER was significantly reduced in all groups compared to A (p <.0001) with Group D (combined therapy) displaying markedly lower ER expression than with either therapy alone (p =.0002). There were significantly raised levels of tumour GLA and metabolites in the two groups (B and D) receiving GLA (p <.0001). This xenograft model of ER+ve breast cancer has demonstrated significantly lower tumour ER expression in those groups receiving GLA, an effect which appears to be additive to the reduced ER expression resulting from tamoxifen alone. The effects of GLA on ER function and the possibility of synergistic inhibitory action of GLA with tamoxifen via enhanced down-regulation of the ER pathway require further investigation. © 2001 Wiley-Liss, Inc.

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