Fatty acid synthase (FASN) can act as a prostate cancer oncogene in mouse models.
FASN, a key enzyme in the synthesis of long-chain fatty acids, is overexpressed in prostate cancer, relative to its expression in adjacent normal tissue. Additionally, previous studies showed that inhibition of FASN activity promoted programmed cell death in prostate cancer cell lines.
In the current study, Massimo Loda, M.D., of the Dana-Farber Cancer Institute in Boston, and colleagues overexpressed FASN in a variety of prostate cancer and precancerous cell lines.
Overexpression of FASN increased cell proliferation and substrate-independent growth. When immortalized prostate epithelial cells that expressed both FASN and the androgen receptor were injected into immunodeficient mice, the cells gave rise to invasive cancer. Inhibition of FASN gene expression led to programmed cell death in a prostate cancer cell line grown in culture. FASN expression showed an inverse correlation with the rate of programmed cell death in prostate cancer biopsy samples.
"The experimental evidence we provide on the oncogenic role of FASN in the prostate suggests that pharmacological targeting of FASN might represent an effective treatment for prostate cancer," the authors write.
The research is published in the March 24 online issue of the Journal of the National Cancer Institute.
- Toshiro Migita, Stacey Ruiz, Alessandro Fornari, Michelangelo Fiorentino, Carmen Priolo, Giorgia Zadra, Fumika Inazuka, Chiara Grisanzio, Emanuele Palescandolo, Eyoung Shin, Christopher Fiore, Wanling Xie, Andrew L. Kung, Phillip G. Febbo, Aravind Subramanian, Lorelei Mucci, Jing Ma, Sabina Signoretti, Meir Stampfer, William C. Hahn, Stephen Finn, and Massimo Loda. Fatty Acid Synthase: A Metabolic Enzyme and Candidate Oncogene in Prostate Cancer. Journal of the National Cancer Institute, 2009; DOI: 10.1093/jnci/djp030
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