Retinol metabolism and lecithin:retinol acyltransferase levels are reduced in cultured human prostate cancer cells and tissue specimens.

Recent studies from our laboratory have indicated that the metabolism of vitamin A (retinol) to retinyl esters, carried out primarily by the enzyme lecithin:retinol acyltransferase (LRAT), is greatly reduced in human carcinoma cell lines of the oral cavity, skin, breast, and kidney as compared with their normal epithelial counterparts. These studies suggest that human carcinoma cells are retinoid-deficient relative to normal epithelial cells. In this study, we examined the metabolism of [(3)H]retinol and [(3)H]retinoic acid (RA) in human prostate cancer lines and in primary cultures of human prostate epithelial cells. Normal cells esterified all of the [(3)H]retinol added to the cultures. In contrast, all seven prostate cancer cell lines and four primary cultures derived from prostatic adenocarcinomas metabolized only trace amounts of [(3)H]retinol to [(3)H]retinyl esters. Correlated with this relative lack of esterification of [(3)H]retinol by the cancer cells was loss of expression of LRAT protein, whereas normal cells expressed abundant levels of LRAT protein by Western analysis. The metabolism of [(3)H]RA was also examined in these prostatic cells. Two of the prostate cancer tumor lines, DU 145 and PJ-1, exhibited rapid metabolism of [(3)H]RA; in contrast, the other tumor lines or primary cultures metabolized [(3)H]RA at a much slower rate. We also found that the immortalization of normal human prostatic epithelial cells by SV40 T antigen led to a reduction in LRAT protein expression and esterification of [(3)H]retinol. Further transformation to tumorigenicity with the ras oncogene resulted in loss of detectable LRAT expression. Finally, we analyzed LRAT protein expression in tissue sections from six prostatectomy specimens by immunohistochemistry. LRAT protein was predominantly expressed in the basal cells of normal prostatic epithelium, whereas its expression was lost in prostate cancer. Collectively, these data implicate aberrant retinoid metabolism in the process of prostatic carcinogenesis.

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