1. ¹Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, IL, USA
2. ²Akita Red Cross Hospital, Akita city, Japan
3. ³Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA

Correspondence: K Watabe, Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, 801 N. Rutledge Street, Springfield, IL 62702, USA. E-mail: kwatabe@siumed.edu

Received 3 July 2004; Revised 14 December 2004; Accepted 24 January 2005; Published online 16 May 2005.

Abstract

Fatty acid synthase (FAS), a key enzyme of the fatty acid biosynthetic pathway, has been shown to be overexpressed in various types of human cancer and is, therefore, considered to be an attractive target for anticancer therapy. However, the exact mechanism of overexpression of the FAS gene in tumor cells is not well understood. In this report, we demonstrate that the expression of the tumor suppressor gene PTEN has a significant inverse correlation with FAS expression in the case of prostate cancer in the clinical setting, and inhibition of the PTEN gene leads to the overexpression of FAS in vitro. We also found that the combination of the expression status of these two genes is a better prognostic marker than either gene alone. Furthermore, our results indicate that the specific inhibition of FAS gene by siRNA leads to apoptosis of prostate tumor cells, and inhibition of PI 3-kinase pathway synergizes with FAS siRNA to enhance tumor cell death. These results provide a strong rationale for exploring the therapeutic use of an inhibitor of the PTEN signaling pathway in conjunction with the FAS siRNA to inhibit prostate tumor growth.