The
progesterone receptor (PR) with its
isoforms and
ligands are involved in breast
tumorigenesis and prognosis. We aimed at analyzing the respective contribution of PR
isoforms, PRA and PRB, in
breast cancer cell proliferation in a new
estrogen-independent cell based-model, allowing independent PR
isoforms analysis. We used the bi-inducible human
breast cancer cell system MDA-iPRAB. We studied the effects and molecular mechanisms of action of
progesterone (P4) and
ulipristal acetate (UPA), a new selective
progesterone receptor modulator, alone or in combination. P4 significantly stimulated MDA-iPRA expressing cells proliferation. This was associated with P4-stimulated expression of the anti-apoptotic factor BCL2-L1 and enhanced recruitment of PRA, SRC-1 and
RNA Pol II onto the +58 kb PR binding motif of the BCL2-L1 gene. UPA decreased cell proliferation and repressed BCL2-L1 expression in the presence of PRA, correlating with PRA and SRC1 but not
RNA Pol II recruitment. These results bring new information on the mechanism of action of PR
ligands in controlling
breast cancer cell proliferation through PRA in an
estrogen independent model. Evaluation of PR
isoforms ratio, as well as molecular signature studies based on PRA target genes could be proposed to facilitate personalized
breast cancer therapy. In this context, UPA could be of interest in endocrine
therapy. Further confirmation in the clinical setting is required.