The toxicity of high levels of NO implies that the enzyme must be tightly regulated starting by transcription, which is only induced in response to stimulation by immune cytokines, bacterial compounds, etc. In a breast cancer cell line expressing the progesterone receptor (PgR+), progesterone (Pg) was found to increase cytokine activation of iNOS, while it has not effect in PgR− cells. This evidence concerns the gene JUP and breast cancer.