CLA reduces breast cancer cell growth and invasion through ERα and PI3K/Akt pathways

We previously reported that conjugated linoleic acid (CIA), a naturally occurring fatty acid, inhibits the growth of ER alpha(+) MCF-7 and ER alpha(-) MDA-MB-231 human breast cancer cells by negative modulation of the ERK/MAPK pathway and apoptosis induction. Here we show that in these cell lines CIA also down-regulates the PI3K/Akt cascade. In MCF-7 cells CLA also triggers ER alpha/PP2A complex formation reducing the phosphorylation state and transcriptional activity of Era whereas in MDA-MB-231 cells CIA does not induce PP2A activation. Moreover, CLA induces the expression of proteins involved in cell adhesion and inhibits cell migration and MMP-2 activity. These findings suggest that CIA may induce the down-regulation of ERa signalling and the reduction of cell invasion through the modulation of balancing between phosphatases and kinases. (C) 2009 Elsevier Ireland Ltd. All rights reserved.