Targeting fatty acid synthase: potential for therapeutic intervention in her-2eu-overexpressing breast cancer.

摘要

Fatty acid synthase (FAS)-catalyzed de novo fatty acid biosynthesis, an anabolic energy-storage pathway largely considered of minor importance in humans, actively contributes to the cancer phenotype by virtue of its ability to specifically regulate the expression and activity of Her-2eu (erbB-2) oncogene. First, a positive correlation between high levels of FAS expression and/or activity and the amplification and/or overexpression of Her-2eu oncogene exists in human breast cancer cell lines. Second, Her-2eu overexpression stimulates the activity of FAS gene promoter and ultimately mediates increased endogenous fatty acid biosynthesis, while this Her-2eu-induced upregulation of breast cancer-associated FAS is inhibitable by anti-Her-2eu antibodies such as trastuzumab (Herceptin(TM)). Third, pharmacological inhibition of FAS activity negatively regulates the expression and tyrosine-kinase activity of Her-2eu-coded p185(Her-2eu) oncoprotein.