LOSS OF FATTY-ACID DELTA(6) DESATURATING ABILITY IN HUMAN MAMMARY EPITHELIAL-CELLS THAT EXPRESS AN ACTIVATED C-HA-RAS ONCOGENE

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 alpha-linolenic acid. Thi s observation, combined with reports that many tumors and tumor cell l ines are deficient in Delta(6) desaturation and/or contain low levels of 6-desaturated EFAs, has led to the suggestion that loss of Delta(6) desaturating ability is relevant to the process of malignant transfor mation. This study was undertaken in search of direct evidence that ma lignant transformation of mammary epithelial cells alters EFA metaboli sm. 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 l ines in terms of ability to convert EFAs (30 mu M) to other EFAs of th e same family. MCF-10AneoT cells lose the ability to perform Delta(6) and Delta(4) desaturations, whereas MCF-10AneoN cells and the SV40 T a ntigen-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, suggestin g that FA metabolism alone cannot account for the effects of EFAs on t he growth of neoplastic and non-neoplastic mammary epithelial cells.