Cytoplasmic retinoic acid-binding protein in retinoic acid-resistant human breast cancer sublines.

Two sublines resistant to the growth-inhibitory effects of retinoic acid (RA) have been isolated from the parental Hs578T wild-type (W.T.) human breast cancer cell line. These sublines (Hs578T-R-1 and Hs578T-R-2) have been growing normally in 10 microM RA during more than 18 months, and their RA-resistant phenotype has remained stable after the removal of RA. The resistance is specific for RA, since their growth is still inhibited by retinol. The intracellular incorporation of [3H]RA is not deficient in the RA-resistant sublines. Cytoplasmic RA-binding protein (cRABP) is present in Hs578T-R-1 and in Hs578T-R-2 and is not different in terms of maximum binding capacity or binding affinity from cRABP in Hs578T (W.T.). These results indicate that RA resistance in these sublines is not secondary to a defect of RA uptake or of binding of RA to cRABP; the resistance may result from a defect distal to binding to cRABP, or alternatively, cRABP may not mediate this effect of RA.