Modulation of IGF-2 expression during growth and differentiation of human neuroblastoma cells: Retinoic acid may induce IGF-2

Insulin-like growth factor 2 (IGF-2) is the major autocrine growth factor for neuroblastoma. IGF-2 mRNA can just be detected in SK-N-BE(2) cell line; higher levels are present in two clones derived from it [BE(2)-C; BE(2)-M17]. IGF-2 mRNA is increased by retinoic acid (RA) only in the clones. IGF-2 expression/induction is more marked in BE(2)-M17, which shows more RA-resistance (evaluated as growth inhibition, neurite outgrowth and induction of programmed cell death). Under RA exposure, the parental line shows a more pronounced growth inhibition, neurite outgrowth and programmed cell death, as compared to its clones. BE(2)-C cells also express type 1 IGF receptor mRNA, though with a different time course than for expression of IGF-2. The data suggest that IGF-2 expression is correlated with growth, and may counteract the growth retardation, neurite outgrowth and programmed cell death effects of retinoic acid. Therefore the autocrine pattern of IGF-2 production by neuroblastoma cells may promote RA-resistance.