Journal
BREAST CANCER RESEARCH AND TREATMENT
Volume 131, Issue 1, Pages 49-63Publisher
SPRINGER
DOI: 10.1007/s10549-011-1394-5
Keywords
Proliferation; Differentiation; Microarrays; Normal breast cells; Glucorticoid; Glucocorticoid receptor silencing; Antiglucocorticoid; Antiprogestin; VA-2914; FAS; IEX-1
Categories
Funding
- INSERM-UPMC
- Association pour la Recherche sur le Cancer
- HRA Pharma
- Novartis (France)
- Institut National Contre le Cancer-INCA
- University of Torino [2007/DT, 2008/DT]
- Regione Piemonte Ricerca Scientifica Applicata [CIPE2004/DT]
- Compagnia di San Paolo, Torino
Ask authors/readers for more resources
The purpose of this article is to determine the tumorigenic potential of estradiol treatment (E2) when combined with either progesterone (P4) or medroxyprogesterone acetate (MPA) in normal luminal human breast cells (HBE) and in human breast cancer cells (T47-D, MCF-7). Proliferation profiles were evaluated, along with the gene transactivation activity between the progesterone and glucocorticoid receptors (PR, GR) in HBE, T47-D, and MCF-7 cells treated by E2 + P4 or E2 + MPA. High throughput transcriptome analysis was performed on RNA from HBE cells treated by E2, E2 + MPA and E2 + P4. GR content was analyzed in normal breast cells as well. In HBE cells, E2 + P4 treatment was antiproliferative and promoted cellular differentiation. In contrast, E2 + MPA displayed mitogenic, antiapoptotic effects in HBE cells and did not influence cellular differentiation. The effect of P4 and MPA on cell proliferation was, however, variable in breast cancer cells. In cells containing GR or/and PR, MPA decreased proliferation whereas P4 antiproliferative effect needed the presence of PR. In HBE cells, the regulation of genes by E2 + P4, and E2 + MPA was significantly different, particularly in cell proliferation and cell death gene families. Further analysis revealed a modulation of the glucocorticoid receptor gene expression pathway by E2 + MPA. Predominant MPA glucocorticoid activity in normal and breast cancer cells was demonstrated using a glucocorticoid antagonist and the down-regulation of the GR by RNA interference. In normal luminal breast cells and in breast cancer cells, P4 and MPA combined with E2 treatment have opposing mitogenic effects due to GR. The consequences of MPA glucocorticoid potencies as well as the importance of GR in breast tissue merit a reappraisal.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available