EXPRESSION OF IGFBP-2, IGFBP-3, AND IGFBP-4 MESSENGER-RNA DURING DIFFERENTIATION OF CACO-2 COLON EPITHELIAL-CELLS

Local production of insulin-like growth factor (IGF)-binding proteins (IGFBP) determines the availability of the IGF to the cell and thus re gulates IGF action. To find out whether specific patterns of IGFBP gen e expression and IGFBP secretion were related to cell growth vs. cell differentiation, expression of IGFBP during long-term culture (21 days , n = 5) of the colon carcinoma cell line Caco-2 was investigated at t he mRNA and protein levels. Markers of cell proliferation (increase in DNA. RNA and protein content) and of differentiation [alkaline phosph atase (AP) activity; creatine kinase (CK) activity] were measured in p arallel during long-term culture. IGFBP-2 mRNA expression correlated s ignificantly with markers of proliferation (P < 0.05), whereas IGFBP-3 mRNA expression or IGFBP-3 secretion correlated with markers of diffe rentiation (AP: r = 0.83, P < 0.001; CK: r = 0.45, P < 0.01). Similarl y, IGFBP-4 mRNA expression correlated significantly with markers of di fferentiation (AP: r = 0.34, P < 0.05; CK: r = 0.35, P < 0.05). We hyp othesize that IGFBP-3 and -4 are related to differentiation of Caco-2 cells, whereas IGFBP-2 is related to proliferation in Caco-2 cells.