Insulin-like growth factor binding protein (IGFBP) gene expression and IGFBP secretion were investigated in a retinoic acid (RA)-resistant subline (RROI) of MCF-7 human breast carcinoma cells. Our results demonstrate that RRO-I cells constitutively secrete higher levels of IGFBP-3 and IGFBP-5. In addition, we found that a 5-fold increase in IGFBP-5 mRNA levels observed in RRO-I cells, which eventually leads to a similar increase in the secreted levels of IGFBP-5, was partly due to an increase in the stability of IGFBP-5 mRNA. Actinomycin D and cycloheximide differentially stabilized IGFBP-5 mRNA in MCF-7 cells but not in RRO-I cells, indicating a difference in the control of IGFBP-5 gene regulation at the level of mRNA stability in these cell lines.