| Autor: |
Recouvreux MS; Área de Investigaciones, Instituto de Oncología, 'Ángel H. Roffo', Av. San Martín 5481, Buenos Aires C1417DTB, Argentina.; Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., Diaz Bessone MI; Área de Investigaciones, Instituto de Oncología, 'Ángel H. Roffo', Av. San Martín 5481, Buenos Aires C1417DTB, Argentina.; Instituto de Nanosistemas, Universidad Nacional de San Martín, 25 de Mayo 1021, San Martín, Buenos Aires 1650, Argentina., Taruselli A; Área de Investigaciones, Instituto de Oncología, 'Ángel H. Roffo', Av. San Martín 5481, Buenos Aires C1417DTB, Argentina., Todaro L; Área de Investigaciones, Instituto de Oncología, 'Ángel H. Roffo', Av. San Martín 5481, Buenos Aires C1417DTB, Argentina., Lago Huvelle MA; Instituto de Nanosistemas, Universidad Nacional de San Martín, 25 de Mayo 1021, San Martín, Buenos Aires 1650, Argentina., Sampayo RG; Department of Bioengineering, University of California, Berkeley, CA 94720, USA., Bissell MJ; Division of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA., Simian M; Área de Investigaciones, Instituto de Oncología, 'Ángel H. Roffo', Av. San Martín 5481, Buenos Aires C1417DTB, Argentina.; Instituto de Nanosistemas, Universidad Nacional de San Martín, 25 de Mayo 1021, San Martín, Buenos Aires 1650, Argentina. |
| Abstrakt: |
To investigate the role of PR isoforms on the homeostasis of stem cells in the normal and neoplastic mammary gland, we used PRA and PRB transgenic mice and the T47D human breast cancer cell line and its derivatives, T47D YA and YB (manipulated to express only PRA or PRB, respectively). Flow cytometry and mammosphere assays revealed that in murine breast, overexpression of PRB leads to an increase in luminal and basal progenitor/stem cells. Ovariectomy had a negative impact on the luminal compartment and induced an increase in mammosphere-forming capacity in cells derived from WT and PRA mice only. Treatment with ICI 182,780 augmented the mammosphere-forming capacity of cells isolated from WT and PRA mice, whilst those from PRB remained unaltered. T47D YB cells showed an increase in the CD44 + /CD24 Low/- subpopulation; however, the number of tumorspheres did not vary relative to T47D and YA, even though they were larger, more irregular, and had increased clonogenic capacity. T47D and YA tumorspheres were modulated by estrogen/antiestrogens, whereas YB spheres remained unchanged in size and number. Our results show that alterations in PR isoform balance have an impact on normal and tumorigenic breast progenitor/stem cells and suggest a key role for the B isoform, with implications in response to antiestrogens. |
