Abstract #1580: Fatty acid synthase phosphorylation as a cancer biomarker Free

During the last decade, increasing interest has developed in fatty acid synthase (FAS) as a potential diagnostic and therapeutic target for human cancer. These notions are based on two fundamental observations: Fatty acid synthase, the enzyme responsible for the de novo synthesis of fatty acids, is highly expressed in most human cancers and its inhibition leads to selective apoptosis of cancer cells both in vitro and in vivo. In addition to its expression in human cancers, it has been shown that FAS also circulates in the blood of patients with breast, prostate, and ovarian cancer and as such, is a potential biomarker for human cancer. FAS elevations have also been found to occur in the blood of obese subjects with non-alcoholic steatohepatitis. Preliminary data has shown that FAS derived from tumor cell lines is phosphorylated on threonine residues while FAS from non-transformed cells is not phosphorylated. The goal of this work is to determine if FAS derived from human cancer is selectively phosphorylated and detectable in the serum of cancer patients. Tumor selective phospho-FAS would form the basis for the development of a cancer-selective FAS ELISA assay. FAS phosphorylation was first investigated in human cancer cell lines. The phosphorylation status of FAS produced from human colon, pancreatic, breast and prostate cancer cell lines was determined with Pro-Q Diamond Phosphoprotein gel stain and western blot analysis of immunoprecipitated FAS using antibodies specific for phosphorylated residues. Specific phosphorylation site(s) on FAS in human cancer cell lines were then identified and sequenced using tandem mass spectroscopy. Phosphorylation sites both common and unique to the individual cell lines will be listed. To determine if FAS circulating in the serum of cancer patients was also modified by phosphorylation, sera from patients with pancreatic, colon, prostate and ovarian cancers containing high levels of FAS were identified using the FASgen FAS ELISA assay. The FAS phosphorylation status of these sera was first assessed by Pro-Q Diamond Phosphoprotein gel stain and then confirmed by western blot analysis of immunoprecipitated FAS using antibodies specific for phosphorylated residues. FAS phosphorylation was detected on multiple residues in the patient sera. These findings could potentially enable the development of a diagnostic ELISA serum test for human cancer based on phosphorylated FAS which would not react with FAS derived from normal tissues such as liver. This tumor selective phospho-FAS would form the basis for the development of a cancer-selective FAS ELISA assay. Measuring phosphorylated and non-phosphorylated FAS levels in the blood may provide a means to distinguish the origin of FAS - from benign or malignant tissue. These data imply that measurement of serum phosphorylated FAS would afford specificity for FAS derived from cancer versus normal tissue.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1580.