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Updated: Mar 6, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
p16 loss rescues functional decline of Brca1-deficient mammary stem cells
Alexandria Scott1,2, Feng Bai1,3, Ho Lam Chan1
1a Molecular Oncology Program, Department of Surgery , Miller School of Medicine, University of Miami , Miami , FL , USA.
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.
Insights
DNA damage repair deficiency impairs mammary stem cell function during aging. Loss of p16Ink4a (p16) prevents this decline, preserving stem cell function and highlighting p16
Area of Science:
- Cellular senescence
- Stem cell biology
- DNA damage repair
Background:
- Accumulated DNA damage can induce senescence, limiting adult stem cell function.
- The link between DNA damage repair deficiency and mammary stem cell functional decline is unclear.
Purpose of the Study:
- To investigate if DNA damage repair deficiency is associated with altered mammary stem cell function.
- To determine the role of p16Ink4a (p16) in age-related mammary stem cell senescence and function.
Main Methods:
- Analysis of senescence markers (p16Ink4a) in aging mammary epithelial cells.
- Evaluation of mammary stem cell function in wild-type and genetically modified mouse models (Brca1, p16 loss).
Main Results:
- Aging induced senescence and increased p16Ink4a expression in mammary epithelial cells.
- Loss of p16 abrogated senescence and enhanced mammary stem cell function.
- Brca1 deficiency induced senescence, p16 expression, and reduced stem cell function, which was rescued by p16 loss.
Conclusions:
- DNA damage repair deficiency is linked to mammary stem cell functional decline.
- p16Ink4a plays a critical role in suppressing Brca1-deficient mammary stem cell function.
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