Vitamin A is required for a number of developmental processes and for the homeostatic maintenance of several adult differentiated tissues and organs. In human
neuroblastoma (NB) cells as well as some other
tumor types, pharmacological doses of
retinoids are able to control growth and induce differentiation in vitro and in vivo. In a search for new genes that are regulated by
retinoids and that contribute to the
biological effects
retinoids have on NB cells, we have isolated five differentially expressed transcripts. Here we report on the characterization of one of them (DD83.1) in NB cell lines. DD83.1 is identical to the human
retSDR1, a
short chain dehydrogenase/reductase that is thought to regenerate
retinol from
retinal in the visual cycle. Its expression is strongly, but differently, regulated by
retinoids in NB cell lines, and it is widely expressed in human tissues, which suggests that it is involved in a more general
retinol metabolic pathway. Both the
retinoic acid-dependent and the exogenous expression of
retSDR1 in SK-N-AS cells induce the accumulation of
retinyl esters, which indicates that it is involved in generating storage forms of
retinol in tissues exposed to physiological
retinol concentrations. We also show that the human
retSDR1 gene, which maps on chromosome 1p36.1, is contained in the
DNA fragment deleted in many NB cell lines bearing MYCN amplification but is conserved in a cell line with a small 1p deletion and normal MYCN. Our observations suggest that
retSDR1 is a novel regulator of
vitamin A metabolism and that its frequent deletion in NB cells bearing MYCN amplification could compromise the sensitivity of those cells to
retinol, thereby contributing to
cancer development and progression.