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ARS Home » Southeast Area » New Orleans, Louisiana » Southern Regional Research Center » Food Processing and Sensory Quality Research » Research » Publications at this Location » Publication #315986
Title: Glyceollin, a novel regulator of mTOR/p70S6 in estrogen receptor positive breast cancer

Author
item BRATTON, MELYSSA - Xavier University
item MARTIN, ELIZABETH - Tulane University
item ELLIOTT, STEVEN - Tulane University
item RHODES, LYNDSAY - Tulane University
item COLLINS-BUROW, BRIDGETTE - Tulane University
item MCLACHLAN, JOHN - Tulane University
item WIESE, THOMAS - Xavier University
item Boue, Stephen

Submitted to: The Journal of Steroid Biochemistry and Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/29/2014
Publication Date: 3/24/2015
Citation: Bratton, M.R., Martin, E.C., Elliott, S., Rhodes, L.V., Collins-Burow, B., Mclachlan, J., Wiese, T., Boue, S.M. 2015. Glyceollin, a novel regulator of mTOR/p70S6 in estrogen receptor positive breast cancer. The Journal of Steroid Biochemistry and Molecular Biology. 150:17-23.

Interpretive Summary: 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, which has anti-estrogen effects in breast cancers. We demonstrate 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 (a) phosphorylation levels. Our data suggests a mechanism for glyceollin inhibition of ER through the induced suppression of a specific enzyme (p70S6), and demonstrates novel mechanisms for ER inhibition.

Technical Abstract: 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, which 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 (a) phosphorylation levels. Additionally, we show that glyceollin suppresses the phosphorylation of proteins known to crosstalk with ER signaling; specifically we demonstrate an inhibition of ribosomal protein S6 kinase, 70 kDa (p70S6) phosphorylation following glyceollin treatment. Our data suggests a mechanism for glyceollin inhibition of ERa through the induced suppression of p70S6, and demonstrates novel mechanisms for ER inhibition.