MT 1 melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells

Abstract

Melatonin inhibits the proliferation of estrogen receptor alpha (ERα)-positive (MCF-7), but not ERα-negative (MDA-MB-231) breast cancer cells. Here, we assessed the effect of MT 1 melatonin receptor stable overexpression in MCF-7 and MDA-MB-231 breast cancer cells on the growth-suppressive effects of melatonin. Parental and vector-transfected MCF-7 cells demonstrated a modest, but significant, growth-suppressive response to melatonin; however, melatonin treatment of MT 1-transfected MCF-7 cells resulted in significantly enhanced growth-suppression. This response was blocked by an MT1/MT2 melatonin receptor antagonist. Interestingly, MT 1-overexpression did not induce a melatonin-sensitive phenotype in melatonin-insensitive MDA-MB-231 cells. Finally, Northern blot analysis demonstrated an enhanced inhibition of ERα mRNA expression and an enhanced induction of pancreatic spasmolytic polypeptide (pS2) by melatonin in MT 1-transfected MCF-7 cells relative to vector-transfected MCF-7 cells. These data suggest the involvement of the MT 1 melatonin receptor in mediation of melatonin effects on growth-suppression and gene-modulation in breast cancer cells.