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.
Bocca
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Department of Experimental Medicine and Oncology, University of Torino, C.so Raffaello 30, 10125 Torino, Italy. claudia.bocca@unito.it
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Cannito
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Colombatto
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Miglietta
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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