Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell Population
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 cytometr...
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MDPI AG
2020-09-01
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| author | María Sol Recouvreux María Inés Diaz Bessone Agustina Taruselli Laura Todaro María Amparo Lago Huvelle Rocío G. Sampayo Mina J. Bissell Marina Simian |
| author_facet | María Sol Recouvreux María Inés Diaz Bessone Agustina Taruselli Laura Todaro María Amparo Lago Huvelle Rocío G. Sampayo Mina J. Bissell Marina Simian |
| author_sort | María Sol Recouvreux |
| collection | DOAJ |
| description | 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<sup>+</sup>/CD24<sup>Low/−</sup> 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. |
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| issn | 2073-4409 |
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| last_indexed | 2024-03-10T16:25:03Z |
| publishDate | 2020-09-01 |
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| spelling | doaj.art-fc3582aad3de48808a19f103b5abf2a42023-11-20T13:20:35ZengMDPI AGCells2073-44092020-09-0199207410.3390/cells9092074Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell PopulationMaría Sol Recouvreux0María Inés Diaz Bessone1Agustina Taruselli2Laura Todaro3María Amparo Lago Huvelle4Rocío G. Sampayo5Mina J. Bissell6Marina Simian7Área de Investigaciones, Instituto de Oncología, “Ángel H. Roffo”, Av. San Martín 5481, Buenos Aires C1417DTB, ArgentinaÁrea de Investigaciones, Instituto de Oncología, “Ángel H. Roffo”, Av. San Martín 5481, Buenos Aires C1417DTB, ArgentinaÁrea de Investigaciones, Instituto de Oncología, “Ángel H. Roffo”, Av. San Martín 5481, Buenos Aires C1417DTB, ArgentinaÁrea de Investigaciones, Instituto de Oncología, “Ángel H. Roffo”, Av. San Martín 5481, Buenos Aires C1417DTB, ArgentinaInstituto de Nanosistemas, Universidad Nacional de San Martín, 25 de Mayo 1021, San Martín, Buenos Aires 1650, ArgentinaDepartment of Bioengineering, University of California, Berkeley, CA 94720, USADivision of Biological Systems and Engineering, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USAÁrea de Investigaciones, Instituto de Oncología, “Ángel H. Roffo”, Av. San Martín 5481, Buenos Aires C1417DTB, ArgentinaTo 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<sup>+</sup>/CD24<sup>Low/−</sup> 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.https://www.mdpi.com/2073-4409/9/9/2074progesterone receptor isoformsmammary glandbreast cancerestrogen receptorstem cells |
| spellingShingle | María Sol Recouvreux María Inés Diaz Bessone Agustina Taruselli Laura Todaro María Amparo Lago Huvelle Rocío G. Sampayo Mina J. Bissell Marina Simian Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell Population Cells progesterone receptor isoforms mammary gland breast cancer estrogen receptor stem cells |
| title | Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell Population |
| title_full | Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell Population |
| title_fullStr | Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell Population |
| title_full_unstemmed | Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell Population |
| title_short | Alterations in Progesterone Receptor Isoform Balance in Normal and Neoplastic Breast Cells Modulates the Stem Cell Population |
| title_sort | alterations in progesterone receptor isoform balance in normal and neoplastic breast cells modulates the stem cell population |
| topic | progesterone receptor isoforms mammary gland breast cancer estrogen receptor stem cells |
| url | https://www.mdpi.com/2073-4409/9/9/2074 |
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