The 12-lipoxygenase gene-transfected MCF-7 human breast cancer cell line exhibits estrogen-independent, but estrogen and omega-6 fatty acid-stimulated proliferation in vitro, and enhanced growth in athymic nude mice.

The estrogen-dependent, linoleic acid (LA)-unresponsive, MCF-7 breast cancer cell line was transfected with 12-lipoxygenase (12-LOX) cDNA (MCF-7/12-LOX cells). The transfectant stably expressed high levels of 12-LOX mRNA and protein, and secreted large quantities of 12-hydroxyeicosatetraenoic acid when cultured with arachidonate. The transfectant grew in vitro in the absence of estrogen, and its growth was stimulated by LA. The MCF-7/12-LOX cells formed small solid tumors when injected into the mammary fat pads of ovariectomized nude mice. Despite this estrogen independence, MCF-7/12-LOX cell growth was stimulated further by estradiol both in vitro and in vivo, and to a greater extent than parental MCF-7 cells.