CLA reduces breast cancer cell growth and invasion through ERalpha and PI3K/Akt pathways.
We previously reported that conjugated linoleic acid (CLA), a naturally occurring fatty acid, inhibits the growth of ERalpha(+) MCF-7 and ERalpha(-) 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 CLA also down-regulates the PI3K/Akt cascade. In MCF-7 cells CLA also triggers ERalpha/PP2A complex formation reducing the phosphorylation state and transcriptional activity of Eralpha whereas in MDA-MB-231 cells CLA 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 CLA may induce the down-regulation of ERalpha signalling and the reduction of cell invasion through the modulation of balancing between phosphatases and kinases.
Department of Experimental Medicine and Oncology, University of Torino, C.so Raffaello 30, 10125 Torino, Italy. claudia.bocca@unito.it
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D044243:Linoleic Acids, Conjugated; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D054648:Protein Phosphatase 2; D020778:Matrix Metalloproteinase 2