The role of sex steroid receptors on lipogenesis in breast and prostate carcinogenesis: a viewpoint.

ABSTRACT

Cancer cells require both nutrients and mitogens to multiply and survive in the unfavorable microenvironment of solid tumors or metastases before angiogenesis. Most cancer cells do not use fatty acids (FA) from the circulation but synthesize them in situ especially to make membranes and lipid signals required for continuously dividing cells. Three lipogenic enzymes are overexpressed, induced by sex steroid hormones and responsible for the in situ increased lipogenesis in cancer cells. We propose that in the early stages of human breast and prostate carcinogenesis, an increased activity of sex steroid receptors is partly responsible for the overexpression of FA synthase (FASN) whose regulation in cancer cells has been particularly studied. Increased activity of androgen receptor (AR), via different mechanisms, was extensively reported in prostate cancer. An increased level/and or activity of progesterone receptors, correlated with an increased expression of FASN, was found both in early stages of breast carcinogenesis and during the hormone replacement therapy of menopausal women. While the majority of recent targeted therapies are based on inhibition of mitogenic pathways, the inhibition of cancer cell nutrition by interfering with lipid synthesis and hormone action should open the way to new therapeutic and preventive approaches of hormone-dependent cancers.