RETINOL ESTERIFICATION IN HEAD AND NECK CANCER

Weill Medical College Of Cornell Univ, New York NY

Investigators

Abstract

Oral cancer (squamous cell carcinoma-SCC) is the sixth most common neoplasm in the world, and has only a 50 percent long term survival rate (Boring et al., 1994). SCCs of the oral cavity have been directly linked to smoking and alcohol use by epidemiological studies. Recent data published from the Gudas laboratory demonstrates a significant decrease in the ability of a variety of SCC cell lines from the oral cavity and skin to metabolize retinol to retinyl esters in comparison to cultured normal human epithelial cell strains. This group has also demonstrated decreased enzymatic conversion of retinol to retinyl esters via lecithin:retinol acyltransferase (LRAT) and dramatically lower LRAT mRNA levels in the tumor cell lines compared to the normal cell strains. Inappropriate cell growth and the loss of normal differentiation characteristic of the tumor cell lines may be, in part, a response to the insufficient internal retinol stored in the ester form. It is now imperative to determine if this relationship between low retinyl ester levels and tumorigenesis also holds true for oral cavity SCCs in an animal model. The experiments proposed in this fellowship will continue these studies in mice, using the carcinogen 4- nitroquinoline-l-oxide to generate tumors in the oral cavity.