Alterations in progesterone receptor isoform balance in normal and neoplastic breast cells modulates the stem cell population

RECOUVREUX; DIAZ BESSONE; TARUSELLI; TODARO; LAGO HUVELLE; SAMPAYO; BISSELL; SIMIAN

Cells

MDPI

Lugar: Tianjin; Año: 2020

2073-4409

To investigate the role of PR isoforms on the homeostasis of stem cells in the normal26 and neoplastic mammary gland, we used PRA and PRB transgenic mice, and the T47D27 human breast cancer cell line and its derivatives, T47D YA and YB. Flow cytometry28 and mammosphere assays revealed that in murine breast overexpression of PRB leads29 to an increase in luminal and basal progenitor/stem cells. Ovariectomy had a negative30 impact on the luminal compartment and induced an increase in mammosphere forming31 capacity in cells derived from WT and PRA mice only. Treatment with ICI 182,78032 augmented the mammosphere forming capacity of cells isolated from WT and PRA33 mice, whilst those from PRB remained unaltered. T47D YB cells showed an increase34 in the CD44+/CD24Low/- subpopulation, however the number of tumorspheres did not35 vary relative to T47D and YA even though they were larger, more irregular and had36 increased clonogenic capacity. T47D and YA tumorspheres were modulated by37 estrogen/anti-estrogens, whereas YB spheres remained unchanged in size and number.38 Our results show that alterations in PR isoform balance have an impact on normal and39 tumorigenic breast progenitor/stem cells and suggest a key role for the B isoform with40 implications on response to anti-estrogens.41