Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma

J Pineal Res. 2013 Apr;54(3):334-45. doi: 10.1111/jpi.12032. Epub 2013 Jan 17.

Abstract

In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast / chemistry
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Carcinoma, Ductal, Breast / chemistry
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism*
  • Female
  • Fibrocystic Breast Disease / chemistry
  • Fibrocystic Breast Disease / genetics
  • Fibrocystic Breast Disease / metabolism
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Real-Time Polymerase Chain Reaction
  • Receptor, Melatonin, MT1 / biosynthesis*
  • Receptor, Melatonin, MT1 / genetics
  • Statistics, Nonparametric

Substances

  • Receptor, Melatonin, MT1