ATRA dose-dependently (0.1–100 μM) inhibited this pathway decreasing IRS-1 concentration in ATRA-sensitive breast cancer lines (MCF-7, T47-D, and ZR75-1) but not in ATRA-resistant cell lines (MDA-MB-231, and MDA-MB-468), and only over-expression of IRS-1 in presence of ATRA reactivated the ATRA-resistance mechanism [135,136]. The gene discussed is IRS1; the disease is breast cancer.