Expression of Insulin-like Growth Factor (IGF)-Il and IGF-I Receptor during Proliferation and Differentiation of

We have studied the expression of insulin-like growth fador type II (IGF-ll) and its autocrine role during the proliferation and differentiation of the CaCo-2 colon carcinoma cell line. ICE-Il RNA levels were high in proliferating cells and decreased by more than 10-fold when cells ceased to proliferate and differentiated. Immunoreadive ICE-Il protein was high in the conditioned media of proliferating cells and decreased 20-fold in the media of differentiated cells. Reduced ICE-Il expression was associated with a decrease in ICE-I receptor number that was high in proliferating cells (approximately 80,000 binding sites/cell) and reduced by 4-fold in differentiated cells. Exogenously added ICE-Il was able to stimulate proliferation of serum-deprived cells in a dose-dependent fashion. ICE-Il aded through the ICE-I receptor, since both basal and ICE-Il-stimulated cell proliferation was inhibited by the monoclonal antibody a-lR3, which blocks the binding sites of the ICE-I receptor. The inhibition of CaCo-2 basal cell growth by the a-lR3 antibody suggeststhat ICE-lI may ad as an autocrine growth fador for these cells.