INSULIN-LIKE GROWTH-FACTORS ACTIVATE ESTROGEN-RECEPTOR TO CONTROL THEGROWTH AND DIFFERENTIATION OF THE HUMAN NEUROBLASTOMA CELL-LINE SK-ER3

The neuroblastoma cell line SK-ER3, which is stably transfected with t he estrogen receptor (ER), was used to study the effect of insulin and insulin-like growth factors (IGF-I and IGF-II) on growth and morpholo gical differentiation induced by estrogens. The data demonstrate that insulin and related growth factors control the growth and morphologica l differentiation of the cell line expressing the ER, but not of the p arental cell line. Effects elicited by the growth factors in SK-ER3 ce lls can be blocked by ER antagonists. Transient transfection studies f urther confirm an effect of the IGFs in modulation of ER-activated pro moters. The results presented support the hypothesis of the existence of cross-talk between membrane and intracellular receptors and provide evidence for physiological consequences of the activation of such a p athway of communication. The present study is of particular interest w ith regard to the theory of prenatal involvement of the ER in maturati on of nerve cells. It could, in fact, be hypothesized that ICE-I and I GF-II, present in high concentrations in the developing brain, might a ctivate the ER expressed in several embryonic brain nuclei.