Breast Cancer Research and Treatment

, Volume 94, Issue 2, pp 161–169 | Cite as

Anti-estrogenic Effects of Conjugated Linoleic Acid through Modulation of Estrogen Receptor Phosphorylation



We previously showed that conjugated linoleic acids (CLA) can inhibit transcriptional activation mediated by estrogen response elements (EREs) and that this activity can, at least in part, account for the reported anti-tumor effects of these compounds on breast cancer cells. Using estrogen receptor positive (ER+) MCF-7 cells, we now demonstrate that CLA inhibited both the transactivation of artificial reporter constructs driven by canonical EREs, and the expression of endogenous progesterone receptors, a gene which is transcriptionally regulated by estrogen through novel ER-binding sites. This inhibition was accompanied by downregulation of ERα expression and decreased ERα–ERE binding activity. These effects on ERα were not causally linked since transfection of an ERα expression plasmid in MCF-7 cells failed to antagonize CLA downregulation of ERα–ERE binding. Immunoprecipitation/Western blot studies revealed that CLA dose-dependently suppressed the degree of phosphorylation of ERα, a modification known to inhibit receptor–ERE interactions. As a mechanism that may account for this induced dephosphorylation of ERα in MCF-7, we found that CLA specifically stimulated protein phosphatase 2A (PP2A) activity. Experiments using the PP2A inhibitor okadaic acid (OA) showed that OA antagonized both the dephosphorylation effects of CLA on ERα and its inhibition of ERα–ERE binding. These results provide evidence that the anti-estrogenic activity of CLA is caused by inducing the dephosphorylation of ERα through stimulation of PP2A activity.


breast cancer conjugated linoleic acid estrogen receptor phosphorylation protein phosphatase 2A 


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Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Department of Gynecology and Obstetrics, Division of ResearchEmory University School of MedicineAtlantaUSA

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