Cited by 693Estrogen and related hormone effectsCancer Cells and MetastasisBreast Cancer Treatment Studies

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Control of mammary stem cell function by steroid hormone signalling

Asselin-Labat, Marie-Liesse, Vaillant, François, Sheridan, Julie M., Pal, Bhupinder, Wu, Di, Simpson, Evan R., Yasuda, Hisataka, Smyth, Gordon K., Martin, T. John, Lindeman, Geoffrey J., Visvader, Jane E.·2010·Nature

DOI 10.1038/nature09027

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Abstract

The ovarian hormones oestrogen and progesterone profoundly influence breast cancer risk, underpinning the benefit of endocrine therapies in the treatment of breast cancer. Modulation of their effects through ovarian ablation or chemoprevention strategies also significantly decreases breast cancer incidence. Conversely, there is an increased risk of breast cancer associated with pregnancy in the short term. The cellular mechanisms underlying these observations, however, are poorly defined. Here we demonstrate that mouse mammary stem cells (MaSCs) are highly responsive to steroid hormone signalling, despite lacking the oestrogen and progesterone receptors. Ovariectomy markedly diminished MaSC number and outgrowth potential in vivo, whereas MaSC activity increased in mice treated with oestrogen plus progesterone. Notably, even three weeks of treatment with the aromatase inhibitor letrozole was sufficient to reduce the MaSC pool. In contrast, pregnancy led to a transient 11-fold increase in MaSC numbers, probably mediated through paracrine signalling from RANK ligand. The augmented MaSC pool indicates a cellular basis for the short-term increase in breast cancer incidence that accompanies pregnancy. These findings further indicate that breast cancer chemoprevention may be achieved, in part, through suppression of MaSC function.

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“The fact that the MaSC pool of the mouse mammary gland was reduced by letrozole treatment [58] further indicates that suppression of MaSC function could be a valuable therapeutic approach in breast cancer.”
BackgroundInfluential
Growth hormone regulates the stem cell population in the growth plate
Chu, N. T. L., Zhou, B., Heinonen, J., Dregval, O. A., Liu, X., Trompet, D., Tian, X., Newton, P. T., Savendahl, L. S., Bendre, A., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2512316122 · Cited by 4
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“Asselin found that mammary stem cells during pregnancy respond strongly to steroid signals and that their temporary increase may be responsible for the more aggressive nature of PPBC (Asselin-Labat et al. 2010).”
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The First AACR Special Conference on Stem Cells, Development, and Cancer: Some of These Cells Are Not Like the Others
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“However, although it has been known that the numbers of basal myoepithelial cells increase 11-fold in the basal compartment during pregnancy (Asselin-Labat et al., 2010), the cellular mechanism underlying basal mammary stem/progenitor cells’ role in driving contractile basket-like architecture…”
Background
Novel insights linking BRCA1-IRIS role in mammary gland development to formation of aggressive PABCs: the case for longer breastfeeding.
Castillo, P., Aisagbonhi, O. A., Saenz, C. C., & ElShamy, W. M. (2022) · PubMed Central · Cited by 4
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“…physiological conditions (Van Keymeulen et al. 2011) and the hormonal in ﬂ uences on the pool size and regenerative activity of mammary stem cells (Asselin-Labat et al. 2010; Joshi et al. 2010) have been revealed by mammary reconstitution assays, using the cleared MFP as the standard site in…”
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Background
Progesterone modulates cell growth via integrin αvβ3-dependent pathway in progesterone receptor-negative MDA-MB-231 cells
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“P 4 often combines with estradiol, a type of estrogen, furthering the proliferation of mammary gland cells [7 – 9, 15 ], and has the capability to activate the tyrosine kinase Src, the extracellular signal-regulated Integrin α v β 3, a cell-surface anchor protein, plays diverse roles in cell…”
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“It has been reported [4] that the density of dense structures such as the milk ducts is similar to the tumor making it difficult to interpret.”
Background
The dynamics of murine mammary stem/progenitor cells
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“Our model may also help explain the limited self-renewal capability observed for MaSCs obtained from pregnant mice (Asselin-Labat et al., 2010) as this pregnancy-associated MaSC pool expansion may result from increased alveolar progenitors, which exhibit limited self-renewal when transplantation…”
Osteoimmunology
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“Darüber hinaus werden RANK und RANKL als Schlüsselmoleküle in der Expansion von Bruststammzellen und in der Entstehung von hormonabhängigem Brustkrebs angesehen (18).”
Background
Anti-RANKL antibody was approved for the treatment of osteoporosis in Japan
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Background
RANK Pathway Inhibition Sensitizes Triple-Negative Breast Cancer to CDK4/6 Inhibitors and Enhances Immune Response
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Background
Reproductive factors and expression of stem cell markers in women with incident benign breast disease
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BackgroundInfluential
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The Proliferative Response to p27 Down-Regulation in Estrogen Plus Progestin Hormonal Therapy is Lost in Breast Tumors
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Authors: Asselin-Labat, M.-L., Vaillant, F., Sheridan, J. M., Pal, B., Wu, D., Simpson, E. R., Yasuda, H., Smyth, G. K., Martin, T. J., Lindeman, G. J., & Visvader, J. E.
Affiliations: Walter and Eliza Hall Institute of Medical Research (AU)
The University of Melbourne (AU)
Monash Medical Centre (AU)
Oriental Yeast Co., Ltd. (Japan) (JP)
St Vincents Institute of Medical Research (AU)
The Royal Melbourne Hospital (AU)
Corresponding author: Lindeman, Geoffrey J.
Visvader, Jane E.
ORCID: Asselin-Labat, Marie-Liesse
Vaillant, François
Sheridan, Julie M.
Pal, Bhupinder
Wu, Di
Simpson, Evan R.
Yasuda, Hisataka
Smyth, Gordon K.
Lindeman, Geoffrey J.
Visvader, Jane E.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2010-04-11
Volume: 465
Issue: 7299
Pages: 798-802
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature09027
OpenAlex: W2117963341
Cited by: 693
References: 38
Citations by year: 2026: 8 · 2025: 16 · 2024: 29 · 2023: 22 · 2022: 29 · 2021: 30 · 2020: 30 · 2019: 32 · 2018: 40 · 2017: 44 · 2016: 45 · 2015: 63 · 2014: 53 · 2013: 64 · 2012: 76
FWCI: 45.37
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords: mammary stem cells, steroid hormone signaling, estrogen, progesterone, RANKL, breast cancer risk, pregnancy, ovariectomy, letrozole, aromatase inhibition, chemoprevention, paracrine signaling, mammary gland development
MeSH terms: Letrozole, Animals, Aromatase, Cell Count, Estrogens, Female, Humans, Mammary Glands, Animal, Nitriles, Ovariectomy, Pregnancy, Pregnancy, Animal, Progesterone, Receptors, Estrogen, Receptors, Progesterone, Stem Cells, Triazoles, Signal Transduction, Integrin beta1, Paracrine Communication, Integrin beta3, Aromatase Inhibitors, Mice, CD24 Antigen, RANK Ligand, ErbB Receptors

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