IN-VITRO PRODUCTION OF LEUKEMIA INHIBITORY FACTOR (LIF) BY HEP G2 HEPATOBLASTOMA CELLS

This study shows that the human hepatoblastoma cell line Hep G2 consti tutively expressed a high level of Leukemia Inhibitory Factor (LIF) mR NA in the characteristic major 3.8 and minor 1.8 Kb forms. DNA analysi s of the LIF gene from Hep G2 revealed no rearrangements. Production a nd secretion of significant concentrations of LIF were demonstrated by enzyme-linked immunoabsorbent assay (ELISA) in culture supernatants o f Hep G2 cells. The highest LIF concentration in culture was found at 48-h (250 pg/ml). LIF produced by Hep G2 cells was biologically active since cell-free culture supernatants were able to induce in vitro dif ferentiation of the M1 murine myeloid leukemia cell line. On the contr ary, no LIF mRNA expression was detected in normal liver cells by PCR analysis. Our results suggest that LIF acts on normal parenchymal hepa tocytes through a paracrine mechanism and on Hep G2 cells by an autocr ine action. Furthermore they indicate that the Hep G2 cell line could be an useful model for studying the LIF autocrine mechanism in hepatom as.