@article{f7e9150cca424b499bff93d75e094ba4,
title = "Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers",
abstract = "Basal-like breast cancers arising in women carrying mutations in the BRCA1 gene, encoding the tumor suppressor protein BRCA1, are thought to develop from the mammary stem cell. To explore early cellular changes that occur in BRCA1 mutation carriers, we have prospectively isolated distinct epithelial subpopulations from normal mammary tissue and preneoplastic specimens from individuals heterozygous for a BRCA1 mutation. We describe three epithelial subsets including basal stem/progenitor, luminal progenitor and mature luminal cells. Unexpectedly, we found that breast tissue from BRCA1 mutation carriers harbors an expanded luminal progenitor population that shows factor-independent growth in vitro. Moreover, gene expression profiling revealed that breast tissue heterozygous for a BRCA1 mutation and basal breast tumors were more similar to normal luminal progenitor cells than any other subset, including the stem cell-enriched population. The c-KIT tyrosine kinase receptor (encoded by KIT) emerged as a key marker of luminal progenitor cells and was more highly expressed in BRCA1-associated preneoplastic tissue and tumors. Our findings suggest that an aberrant luminal progenitor population is a target for transformation in BRCA1-associated basal tumors .",
author = "Elgene Lim and Fran{\c c}ois Vaillant and Di Wu and Forrest, {Natasha C.} and Bhupinder Pal and Hart, {Adam H.} and Asselin-Labat, {Marie Liesse} and Gyorki, {David E.} and Teresa Ward and Audrey Partanen and Frank Feleppa and Huschtscha, {Lily I.} and Thorne, {Heather J.} and Fox, {Stephen B.} and Max Yan and French, {Juliet D.} and Brown, {Melissa A.} and Smyth, {Gordon K.} and Visvader, {Jane E.} and Lindeman, {Geoffrey J.}",
note = "Funding Information: K.U. Wagner (University of Nebraska Medical Center) for MMTV-Cre mice and A. Parlow (National Hormone and Pituitary Program, US National Institute of Diabetes, Digestive and Kidney Diseases) for prolactin. We gratefully acknowledge the invaluable contribution of numerous patients, surgeons, pathologists and tissue bank coordinators, and we thank A. Willems, E. Niedermayr, all kConFab research staff and Family Cancer Clinics and Clinical Follow-Up Study for their contributions to the kConFab resource, as well as the many families who contribute to kConFab. This work was supported by the Victorian Breast Cancer Research Consortium, the Australian National Health and Medical Research Council, the US National Breast Cancer Foundation, the US Department of Defense, the Susan G. Komen Breast Cancer Foundation, the Australian Stem Cell Centre, the Australian Cancer Research Foundation and the Victorian Cancer Biobank. kConFab is supported by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia.",
year = "2009",
month = aug,
doi = "10.1038/nm.2000",
language = "English (US)",
volume = "15",
pages = "907--913",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "8",
}