Retinoic Acid and Estrogen Modulation of Insulin-like Growth Factor Binding Protein-4 Gene Expression and the Estrogen Receptor Status of Human Breast Carcinoma Cells

Retinoic acid (RA) and estrogen modulation of insulin like-growth factor binding protein-4 (IGFBP-4) gene expression was investigated in a number of human breast carcinoma (HBC) cell lines. Our results indicate that RA and/or estrogen modulation of IGFBP-4 mRNA levels appear to correlate with the ER-status of HBC cell lines. RA and estrogen enhanced IGFBP-4 mRNA levels in ER-positive MCF-7, RRO-I and ZR-75 cell lines and the effect of both of these agents in combination was additive. Although both individually also enhanced IGFBP-4 mRNA levels in ER-positive T47D cells, their effect in combination was antagonistic in this cell line. Transfection of human ER into ER-negative MDA-MB-231 cells conferred RA and estrogen the ability to enhance IGFBP-4 mRNA but both agents failed to concomitantly modulate IGFBP-4 levels in the CM suggesting a dual regulation by these agents at transcription/post-transcription and translation/secretion levels.