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

Mol Cell Endocrinol. 2002 Jun 28;192(1-2):147-56. doi: 10.1016/s0303-7207(02)00029-1.

Abstract

Melatonin inhibits the proliferation of estrogen receptor alpha (ERalpha)-positive (MCF-7), but not ERalpha-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 ERalpha 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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / pathology*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Estrogen Receptor alpha
  • Estrogens*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hormone Antagonists / pharmacology
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Melatonin / pharmacology*
  • Mucins*
  • Muscle Proteins*
  • Naphthalenes / pharmacology
  • Neoplasm Proteins / analysis
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / pathology*
  • Neuropeptides*
  • Peptides / genetics
  • Peptides / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Receptors, Cell Surface / antagonists & inhibitors
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / physiology*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Estrogen / analysis
  • Receptors, Melatonin
  • Recombinant Fusion Proteins / physiology
  • Transfection
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / pathology

Substances

  • Estrogen Receptor alpha
  • Estrogens
  • Hormone Antagonists
  • Intercellular Signaling Peptides and Proteins
  • Mucins
  • Muscle Proteins
  • Naphthalenes
  • Neoplasm Proteins
  • Neuropeptides
  • Peptides
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Estrogen
  • Receptors, Melatonin
  • Recombinant Fusion Proteins
  • TFF3 protein, rat
  • Tff2 protein, rat
  • Trefoil Factor-2
  • Trefoil Factor-3
  • N-(2-(1-naphthalenyl)ethyl)cyclobutanecarboxamide
  • pancreatic spasmolytic polypeptide
  • Melatonin