All trans-retinoic acid suppresses in vitro growth and down-regulates LIF gene expression as well as telomerase activity of human medulloblastoma cells

Leukemia inhibitory factor (LIF) is prevalently expressed in human medullob lastomas in vivo and in vitro. Blockage of LIF expression or biological fun ction can inhibit in vitro growth and induce differentiation-like phenotype s of medulloblastoma cells (Med-3), suggesting a redifferentiation potentia l of Med-3 cells when intrinsic dedifferentiation factor(s) is suppressed o r external differentiation element(s) is exerted. All-trans retinoic acid ( RA) can induce differentiation in some types of cancers but its effect on m edulloblastoma cells has not yet been described. To address the above issue s, three dosages (5, 8 and 10 mu mol/L) of RA were used to treat Med-3 cell s and their effects on the target cells were evaluated by multiple approach es. It was found that, in addition to induction of morphological changes an d growth inhibition, RA could repress LIF expression as well as the telomer ase activity of Med-3 cells in time - and dose - related fashions. Our data thus suggest that the growth inhibitory effect of RA on Med-3 cells may be correlated with the LIF down-regulation. Reduction of telomerase activity by RA indicates that this enzymatic activity is a potential differentiation indicator of medulloblastoma cells.