Glyceollin, a novel regulator of mTOR/p70S6 in estrogen receptor positive breast cancer

An estimated 70% of breast cancer tumors utilize estrogen receptor (ER) signaling to maintain tumorigenesis and targeting of the estrogen receptor is a common method of treatment for these tumor types. However, ER-positive (+) breast cancers often acquire drug resistant or altered ER activity in response to anti-estrogens. Here we demonstrate glyceollin, an activated soy compound, has anti-estrogen effects in breast cancers. We demonstrate through estrogen response element luciferase and phosphorylation-ER mutants that the effects of glyceollin arise from mechanisms distinct from conventional endocrine therapies. We show that glyceollin suppresses estrogen response element activity; however, it does not affect ER-alpha phosphorylation levels. Additionally we show that glyceollin suppresses the phosphorylation of proteins known to crosstalk with ER-alpha signaling, specifically we demonstrate an inhibition of Ribosomal Protein S6 Kinase, 70kDa (p70S6) phosphorylation following glyceollin treatment. Our data suggests a mechanism for glyceollin inhibition of ER through the induced suppression of p70S6 and demonstrates novel mechanisms for ER inhibition.