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OBJECTIVES:

Many human epithelial cancers, particularly those with a poor prognosis, express high levels of fatty acid synthase (FASN), a key metabolic enzyme linked to synthesis of membrane phospholipids in cancer cells. Overexpression of FASN is linked with activation of the phosphatidylinositol-3′-kinase (PI3 K)/AKT pathway. However, the role of FASN in colorectal cancer (CRC) has not been fully elucidated. We investigated the expression of FASN and determined its functional association with the PI3/AKT pathway in CRC.

METHODS:

Expression of FASN and its associated targets were studied by immunohistochemistry on 448 CRC tumors in a tissue microarray (TMA) format. Analysis of apoptosis and cell cycle was evaluatedin vitrousing CRC cell lines by flow cytometry and DNA fragmentation assays. Protein expression was determined by immunohistochemistry and western blotting. In vivoxenograft …