Get access

Gender-related invasion differences associated with mRNA expression levels of melatonin membrane receptors in colorectal cancer

Authors

  • Josefa León,

    Corresponding author
    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    • Hospital Universitario San Cecilio, Unidad de Apoyo a la Investigación, Avd. Dr. Oloriz 16, 18012 Granada, Spain.
    Search for more papers by this author
  • Jorge Casado,

    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for more papers by this author
  • Ángel Carazo,

    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for more papers by this author
  • Laura Sanjuán,

    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for more papers by this author
  • Ana Maté,

    1. San Cecilio University Hospital, Granada, Spain
    Search for more papers by this author
  • Paloma Muñoz de Rueda,

    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for more papers by this author
  • Paloma de la Cueva,

    1. Red de Bancos de Tumores de Andalucía (RBTA), Granada, Spain
    Search for more papers by this author
  • Rosa Quiles,

    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for more papers by this author
  • Sergio Ruíz,

    1. San Cecilio University Hospital, Granada, Spain
    Search for more papers by this author
  • Ángela Ruíz-Extremera,

    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for more papers by this author
  • Javier Salmerón

    1. San Cecilio University Hospital, Granada, Spain
    2. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
    Search for more papers by this author

Abstract

Melatonin inhibits growth and invasive capacity of colon cancer cells in vitro through its membrane (MT1 and MT2) and/or nuclear receptors (RORα). Previous studies showed that this indoleamine is present in both the normal and colon cancer at similar levels. Therefore, we analyzed MT1, MT2, and RORα expression in tumor samples versus normal mucosa (NM) from patients suffering from colorectal cancer (CRC). Given the existence of sex differences in the incidence and pathology of CRC and the involvement of steroid receptors in the oncostatic actions of melatonin in some types of cancer, we also analyzed the expression of androgen (AR) and estrogen receptor (ER) α and ERβ. Finally, we conducted some experiments in colon cancer cell lines to corroborate the experiments carried out in human tumors. We found a decreased expression of MT1, MT2, AR, ERα, and ERβ in tumor samples versus NM, but no changes in RORα expression in the whole cohort of patients. Classifying tumors by stage and gender, MT1, MT2, AR, ERα, and ERβ expression decreased in both early stage and advanced tumors, but only in male patients. On the other hand, MT1 and MT2 expression correlated positively with AR, ERα, and ERβ expression in male patients and with ERα or ERβ in female patients. In vitro, the invasive capacity was higher in cells with the least expression of MT1, MT2, and AR, and nonselective MT1/MT2 agonists inhibited cell growth and invasion. These results could indicate a possible interaction of these pathways. © 2011 Wiley Periodicals, Inc.

Get access to the full text of this article

Ancillary