Reduced Lecithin

Abstract

Purpose: Retinoids, which include vitamin A (retinol; ROL) and its derivatives, have been investigated in the treatment of bladder cancer. We have shown that expression of the enzyme lecithin:ROL acyltransferase (LRAT), which converts ROL to retinyl esters, is reduced in several human cancers. Here we evaluated expression of LRAT protein and mRNA in normal and malignant bladder tissue specimens from human patients. We also examined the effect of retinoids on LRAT expression in bladder cancer cell lines.Experimental Design: We evaluated 49 bladder cancer specimens for LRAT protein expression using immunohistochemistry with affinity-purified antibodies to human LRAT. LRAT mRNA expression was assessed using reverse transcription-PCR in bladder specimens from an additional 16 patients. We examined the effect of retinoic acid and ROL on LRAT mRNA expression in five human bladder cancer cell lines.Results: LRAT protein was detected throughout the nonneoplastic bladder epithelium in all of the specimens. In bladder tumors, LRAT protein expression was reduced compared with the nonneoplastic epithelium or was completely absent in 7 of 32 (21.9%) superficial tumors versus 16 of 17 (94.1%) invasive tumors (P < 0.001). All of the nonneoplastic bladder specimens tested (11 of 11) showed LRAT mRNA expression, compared with 5 of 8 (62%) superficial tumors and 0 of 5 (0%) invasive tumors (P ‫؍‬ 0.001). Three of five human bladder cancer cell lines expressed LRAT mRNA independent of retinoid exposure, whereas in two cell lines LRAT mRNA expression was induced by retinoid treatment.Conclusions: We report a significant reduction in LRAT expression in bladder cancer. Moreover, we demonstrate an inverse correlation of LRAT mRNA and protein expression with increasing tumor stage. These data suggest that loss of LRAT expression is associated with invasive bladder cancer.

Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells

“…Lecithin retinol acyltransferase (LRAT), an enzyme responsible for the esterification of retinol to retinyl ester (Ruiz et al, 1999), was suggested to be the founder of the eukaryotic members of this superfamily (Anantharaman and Aravind, 2003). Similar to H-REV107-like proteins, LRAT expression is reduced in several human tumors and in corresponding cell lines (Andreola et al, 2000;Boorjian et al, 2004;Guo et al, 2000;Guo et al, 2001;Guo et al, 2002;Guo and Gudas, 1998;Jurukovski and Simon, 1999;Simmons et al, 2002;Zhan et al, 2003). In contrast to the H-REV107 proteins and most of the prokaryotic related proteins, LRAT has a defined biochemical function and the active motifs within the protein have been characterized (Mondal et al, 2000;Mondal et al, 2001;Xue and Rando, 2004).…”

Lecithin retinol acyltransferase as a potential prognostic marker for malignant melanoma

“…Reduced expression of LRAT has been found in different types of cancer, for example bladder, kidney, prostate, breast and oral cavity (13)(14)(15)(16). In bladder cancer, LRAT protein expression correlated with tumor stage of the primary; in most invasive tumors, it was absent (14). This matches the finding that LRAT might have tumor-suppressor properties (17).…”

Differential gene expression profiles of radioresistant pancreatic cancer cell lines established by fractionated irradiation

“…The esterification of retinoids to retinyl esters is an important mechanism for maintaining tissue retinoids in a form that is easily stored and readily mobilized for additional metabolic needs (39). Recent reports have indicated there is a significant reduction in lecithin retinol acyltransferase expression in cancer compared with normal tissues, as well as an inverse correlation of this expression with increasing tumor stage (40). Therefore, restoration of lecithin retinol acyltransferase expression may be a reasonable strategy for cancer therapy.…”