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

Abstract

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-2/neu (erbB-2) oncogene. First, a positive correlation between high levels of FAS expression and/or activity and the amplification and/or overexpression of Her-2/neu oncogene exists in human breast cancer cell lines. Second, Her-2/neu overexpression stimulates the activity of FAS gene promoter and ultimately mediates increased endogenous fatty acid biosynthesis, while this Her-2/neu-induced upregulation of breast cancer-associated FAS is inhibitable by anti-Her-2/neu antibodies such as trastuzumab (Herceptin(TM)). Third, pharmacological inhibition of FAS activity negatively regulates the expression and tyrosine-kinase activity of Her-2/neu-coded p185(Her-2/neu) oncoprotein.

• Authors: Javier A Menendez, Ruth Lupu, Ramon Colomer
• Journal: Drug news & perspectives (Drug News Perspect) 2005 Jul-Aug Vol. 18 Issue 6 Pg. 375-85 ISSN: 0214-0934 [Print] United States
• PMID: 16247515 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: Copyright 2005 Prous Science. All rights reserved.

Chemical References

• Antineoplastic Agents
• Cerulenin
• alpha-methylene gamma-butyrolactone
• Catechin
• epigallocatechin gallate
• Fatty Acid Synthases
• Receptor, ErbB-2
• 4-Butyrolactone

Topics

• 4-Butyrolactone (administration & dosage, analogs & derivatives)
• Animals
• Antineoplastic Agents (administration & dosage)
• Breast Neoplasms (drug therapy, genetics, metabolism, prevention & control)
• Catechin (administration & dosage, analogs & derivatives)
• Cerulenin (administration & dosage)
• Drug Delivery Systems
• Fatty Acid Synthases (antagonists & inhibitors, biosynthesis, metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lipid Metabolism (drug effects)
• Receptor, ErbB-2 (antagonists & inhibitors, genetics, metabolism)