p16 loss rescues functional decline of Brca1-deficient mammary stem cells

Alexandria Scott, Feng Bai, Ho Lam Chan, Shiqin Liu, Joyce M Slingerland, David J Robbins, Anthony J Capobianco, Xin-Hai Pei

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Recent evidence indicates that the accumulation of endogenous DNA damage can induce senescence and limit the function of adult stem cells. It remains elusive whether deficiency in DNA damage repair is associated with the functional alteration of mammary stem cells. In this article, we reported that senescence was induced in mammary epithelial cells during aging along with increased expression of p16Ink4a (p16), an inhibitor of CDK4 and CKD6. Loss of p16 abrogated the age-induced senescence in mammary epithelial cells and significantly increased mammary stem cell function. We showed that loss of Brca1, a tumor suppressor that functions in DNA damage repair, in the mammary epithelium induced senescence with induction of p16 and a decline of stem cell function, which was rescued by p16 loss. These data not only answer the question as to whether deficiency in DNA damage repair is associated with the functional decline of mammary stem cells, but also identify the role of p16 in suppressing Brca1-deficient mammary stem cell function.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalCell Cycle
DOIs
StateAccepted/In press - Mar 10 2017

Fingerprint

Breast
Stem Cells
DNA Damage
DNA Repair
Epithelial Cells
Adult Stem Cells
Cell Aging
Epithelium
Neoplasms

Keywords

  • Brca1
  • p16
  • senescence
  • stem cell function

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

p16 loss rescues functional decline of Brca1-deficient mammary stem cells. / Scott, Alexandria; Bai, Feng; Chan, Ho Lam; Liu, Shiqin; Slingerland, Joyce M; Robbins, David J; Capobianco, Anthony J; Pei, Xin-Hai.

In: Cell Cycle, 10.03.2017, p. 1-6.

Research output: Contribution to journalArticle

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AU - Capobianco, Anthony J

AU - Pei, Xin-Hai

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