Proposed mechanism of CLA action in SKBr3 cells.

<p>(A) This scenario describes a direct effect on IKK by t10c12 CLA. A consequence of IKK inhibition is reduced phosphorylation of IκB and nuclear localization of p65. A decrease in COX2-derived PGE₂ synthesis will result in loss of HER2 (as described in by Benoit et al, Oncogene, 2004; 23(8):1631). (B) This scenario describes a direct effect on HER2 protein by t10c12 CLA. In this scenario, HER2 is dissociated from the plasma membrane and targeted for ubiquitination and proteosomal degradation. Loss of HER2 signaling downregulates PI-3 kinase and IKK activity. NFκB is sequestered in the cyotosol by IκB and its target genes such as COX2 are not transcribed.