Retinoid receptors: pathways of proliferation inhibition and apoptosis induction in breast cancer cell lines.

In this study we investigated the effects of several selective agonist retinoids (specific for RARα, RARβ, RARγ, and RXRα, respectively) on the proliferation and apoptosis of human breast cancer cell lines All these retinoids inhibit proliferation through apoptosis induction, but with some differences among the tested molecules and the three cell lines. In particular, estrogen receptor positive (ER+) cells display a higher sensitivity to RARs selective compounds, the RARα selective compound being the most effective agent, while estrogen receptor negative (ER-) cells show a greater responsiveness to the RXRα selective retinoid. In all tested cell lines a potent antiproliferative and apoptotic effect was also displayed by a high dose of the RARy selective compound. The apoptosis induction is associated with bcl-2 down-regulation, while p53 expression is not modified by any retinoid. Only in one cell line (ZR-75.1), after RARα selective retinoid treatment is there an induction of RARβ: therefore not only RARβ induction but also other mechanisms may contribute to the growth inhibitory effect of retinoids in tested breast cancer cell lines.