Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate
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Gupta_Genetic predisposition.pdf
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Author(s)
Proia, Theresa A.
Keller, Patricia J.
Klebba, Ina
Jones, Ainsley D.
Sedic, Maja
Gilmore, Hannah
Tung, Nadine
Naber, Stephen P.
Schnitt, Stuart
Gupta, Piyush
Date Issued
February 2011
Journal
Cell Stem Cell
Publisher
Elsevier
Citation
Proia, Theresa A., Patricia J. Keller, Piyush B. Gupta, Ina Klebba, Ainsley D. Jones, Maja Sedic, Hannah Gilmore, Nadine Tung, Stephen P. Naber, and Stuart Schnitt. “Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate.” Cell Stem Cell 8, no. 2 (February 4, 2011): 149-163. Copyright © 2011 Elsevier Inc.
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Final published version
Abstract
Women with inherited mutations in the BRCA1 gene have increased risk of developing breast cancer but also exhibit a predisposition for the development of aggressive basal-like breast tumors. We report here that breast epithelial cells derived from patients harboring deleterious mutations in BRCA1 (BRCA1[superscript mut/+]) give rise to tumors with increased basal differentiation relative to cells from BRCA1[superscript +/+] patients. Molecular analysis of disease-free breast tissues from BRCA1[superscript mut/+] patients revealed defects in progenitor cell lineage commitment even before cancer incidence. Moreover, we discovered that the transcriptional repressor Slug is an important functional suppressor of human breast progenitor cell lineage commitment and differentiation and that it is aberrantly expressed in BRCA1[superscript mut/+] tissues. Slug expression is necessary for increased basal-like phenotypes prior to and after neoplastic transformation. These findings demonstrate that the genetic background of patient populations, in addition to affecting incidence rates, significantly impacts progenitor cell fate commitment and, therefore, tumor phenotype.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.stem.2010.12.007
