Evidence that an early pregnancy causes a persistent decrease in the number of functional mammary epithelial stem cells - Implications for pregnancy-induced protection against breast cancer

Stefan K. Siwko, Jie Dong, Michael T. Lewis, Hao Liu, Susan G. Hilsenbeck, Yi Li

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

A completed pregnancy at a young age reduces a woman's lifetime risk of breast cancer by up to 50%. A similar protective effect of an early pregnancy has been observed in rodent models using chemical carcinogens. However, the mechanisms responsible for this protective effect remain unclear. Stem cells have been proposed to be the cells of origin for breast cancer. We hypothesized that an early pregnancy reduces adult levels of either mammary stem cells or mammary multipotent progenitor cells. Unsorted mammary cells from adult mice that had undergone an early parity had the same mammosphere formation efficiency as cells from age-matched virgin mice. However, when we transplanted adult mammary cells in limiting dilutions into cleared fat pads of syngeneic mice, we found a significant reduction in the outgrowth potential of the cells from early parous mice compared with age-matched virgin mice. The extent of fat pad filling in successful outgrowths did not change, suggesting that although mammary stem cells in parous mice retained their functional competence, the number of mammary stem cells was reduced. Our results provide the first direct evidence that an early pregnancy has an effect on mammary stem cells.

Original languageEnglish (US)
Pages (from-to)3205-3209
Number of pages5
JournalStem Cells
Volume26
Issue number12
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

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Breast
Stem Cells
Epithelial Cells
Breast Neoplasms
Pregnancy
Adipose Tissue
Chemical Models
Parity
Carcinogens
Mental Competency
Rodentia

Keywords

  • Epithelial cells
  • Mammary glands
  • Pregnancy
  • Stem cell transplantation
  • Stem cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Evidence that an early pregnancy causes a persistent decrease in the number of functional mammary epithelial stem cells - Implications for pregnancy-induced protection against breast cancer. / Siwko, Stefan K.; Dong, Jie; Lewis, Michael T.; Liu, Hao; Hilsenbeck, Susan G.; Li, Yi.

In: Stem Cells, Vol. 26, No. 12, 01.12.2008, p. 3205-3209.

Research output: Contribution to journalArticle

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