Glucocorticoid receptor changes its cellular location with breast cancer development
Isabel Conde1, Ricardo Paniagua1, Benito Fraile1, Javier Lucio2 and Maria I. Arenas1
1Department of Cell Biology and Genetics, and 2Department of Physiology. University of Alcalá, Alcalá de Henares, Madrid. Spain.
Offprint requests to: Dr. M.I. Arenas, Department of Cell Biology and Genetics, University of Alcalá, 28871 Alcalá de Henares, Madrid, Spain. e-mail: misabel.arenas@uah.es
Summary. Glucocorticoids play a major role in attenuation of the inflammatory response and they are useful in the primary combination chemotherapy of breast cancer, since in vitro studies have demonstrated an antiproliferative effect in human breast cancer cells. In contrast, it was recently shown that glucocorticoids protect against apoptotic signals evoked by cytokines, cAMP, tumour suppressors, and death genes in mammary gland epithelia. Their actions are mediated by intracellular receptor (GR) that functions as a hormone-dependent transcription factor; however, no previous studies have been focused on GR expression in different pathologies of the human breast, and the possible relationship with that of mineralocorticoid receptor (MR) and COX-2. Also, the role of these proteins on tumoral breast epithelial cells remains unclear. Therefore, we examined GR, MR and COX-2 expression by immunohistochemistry and Western blot techniques in 142 samples of human breast obtained by total or partial mastectomy. We found that the percentage of positive patients presenting nuclear immunoreaction to GR decreased with tumor development, while all samples analyzed showed cytoplasmic immunoreactions to MR. All positive samples to COX-2 antibody showed cytoplasmic location, a higher immunoreaction being observed in benign breast diseases than in carcinomatous lesions. Thus, breast cancer progression is associated with the accumulation of GR in the cytoplasm of tumoral cells and the decrease of COX-2 expression. Histol Histopathol 23, 77-85 (2008)
Key words: GR, MR, COX-2, Breast cancer
DOI: 10.14670/HH-23.77