Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate
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 (B...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/84488 https://orcid.org/0000-0002-9703-1780 |
| _version_ | 1826195465419358208 |
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| author | Proia, Theresa A. Keller, Patricia J. Klebba, Ina Jones, Ainsley D. Sedic, Maja Gilmore, Hannah Tung, Nadine Naber, Stephen P. Schnitt, Stuart Gupta, Piyush Kuperwasser, Charlotte Lander, Eric Steven |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Proia, Theresa A. Keller, Patricia J. Klebba, Ina Jones, Ainsley D. Sedic, Maja Gilmore, Hannah Tung, Nadine Naber, Stephen P. Schnitt, Stuart Gupta, Piyush Kuperwasser, Charlotte Lander, Eric Steven |
| author_sort | Proia, Theresa A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:13:06Z |
| format | Article |
| id | mit-1721.1/84488 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T10:13:06Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/844882022-09-26T16:31:43Z Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate Proia, Theresa A. Keller, Patricia J. Klebba, Ina Jones, Ainsley D. Sedic, Maja Gilmore, Hannah Tung, Nadine Naber, Stephen P. Schnitt, Stuart Gupta, Piyush Kuperwasser, Charlotte Lander, Eric Steven Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Gupta, Piyush Lander, Eric S. 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. 2014-01-24T15:39:31Z 2014-01-24T15:39:31Z 2011-02 2010-08 Article http://purl.org/eprint/type/JournalArticle 19345909 http://hdl.handle.net/1721.1/84488 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. https://orcid.org/0000-0002-9703-1780 en_US http://dx.doi.org/10.1016/j.stem.2010.12.007 Cell Stem Cell 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. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Proia, Theresa A. Keller, Patricia J. Klebba, Ina Jones, Ainsley D. Sedic, Maja Gilmore, Hannah Tung, Nadine Naber, Stephen P. Schnitt, Stuart Gupta, Piyush Kuperwasser, Charlotte Lander, Eric Steven Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate |
| title | Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate |
| title_full | Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate |
| title_fullStr | Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate |
| title_full_unstemmed | Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate |
| title_short | Genetic Predisposition Directs Breast Cancer Phenotype by Dictating Progenitor Cell Fate |
| title_sort | genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate |
| url | http://hdl.handle.net/1721.1/84488 https://orcid.org/0000-0002-9703-1780 |
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