Potentiation of EGF signaling by estrogen in breast cancer cells has been shown to involve transactivation of EGFR by receptors for sphingosine 1-phosphate (S1P), a bioactive phospholipid generated by the phosphorylation of sphingosine by sphingosine kinases 1 and 2 (SphK1 and SphK2) [48]. This evidence concerns the gene EGFR and breast cancer.