Loss of fatty acid Δ6 desaturating ability in human mammary epithelial cells that express an activated c-Ha-ras oncogene

S. I. Grammatikos, M. J. Harvey, P. V. Subbaiah, T. A. Victor, William M Miller*

*Corresponding author for this work

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The synthesis of essential fatty acids (EFAs) that have been shown to inhibit breast cancer cell growth in vitro and tumor growth in animals requires desaturation at C-6 of linoleic or α-linolenic acid. This observation, combined with reports that many tumors and tumor cell lines are deficient in Δ6 desaturation and/or contain low levels of 6-desaturated EFAs, has led to the suggestion that loss of Δ6 desaturating ability is relevant to the process of malignant transformation. This study was undertaken in search of direct evidence that malignant transformation of mammary epithelial cells alters EFA metabolism. We used two cell lines derived from the spontaneously immortalized human mammary epithelial cell line MCF-10A and expressing either the c-Ha-ras protooncogene (MCF-10AneoN) or an activated c-Ha-ras oncogene (MCF-10AneoT), and a cell line immortalized by transfection of human mammary epithelial cells with SV40 T antigen. We compared these cell lines in terms of ability to convert EFAs (30 μM) to other EFAs of the same family. MCF-10AneoT cells lose the ability to perform Δ6 and Δ4 desaturations, whereas MCF-10AneoN cells and the SV40 T antigen-transformed cell line do not. No significant changes in growth response to culture with 6-desaturated EFAs were noted for MCF-10AneoT cells compared with MCF-10AneoN and parental MCF-10A cells, suggesting that FA metabolism alone cannot account for the effects of EFAs on the growth of neoplastic and non-neoplastic mammary epithelial cells.

Original languageEnglish (US)
Pages (from-to)1039-1046
Number of pages8
JournalInternational Journal of Oncology
Volume6
Issue number5
StatePublished - Jan 1 1995

Keywords

  • Breast cancer
  • Cell culture
  • Dietary fat
  • Essential fatty acid
  • Fatty acid metabolism

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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