Publication Date:
2010-04-13
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Asselin-Labat, Marie-Liesse -- Vaillant, Francois -- Sheridan, Julie M -- Pal, Bhupinder -- Wu, Di -- Simpson, Evan R -- Yasuda, Hisataka -- Smyth, Gordon K -- Martin, T John -- Lindeman, Geoffrey J -- Visvader, Jane E -- England -- Nature. 2010 Jun 10;465(7299):798-802. doi: 10.1038/nature09027. Epub 2010 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20383121" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, CD24/metabolism
;
Antigens, CD29/metabolism
;
Aromatase/metabolism
;
Aromatase Inhibitors/pharmacology
;
Cell Count
;
Estrogens/*metabolism/pharmacology
;
Female
;
Humans
;
Integrin beta3/metabolism
;
Mammary Glands, Animal/*cytology
;
Mice
;
Nitriles/pharmacology
;
Ovariectomy
;
Paracrine Communication/drug effects
;
Pregnancy
;
Pregnancy, Animal/physiology
;
Progesterone/antagonists & inhibitors/*metabolism/pharmacology
;
RANK Ligand/metabolism
;
Receptor, Epidermal Growth Factor/metabolism
;
Receptors, Estrogen/deficiency
;
Receptors, Progesterone/deficiency
;
Signal Transduction/drug effects
;
Stem Cells/*cytology/drug effects/metabolism
;
Triazoles/pharmacology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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