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 .
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors: Elgene
authors: E
authors: Lim
authors: François
authors: F
authors: Vaillant
authors: Di
authors: D
authors: Wu
authors: Natasha C
authors: NC
authors: Forrest
authors: Bhupinder
authors: B
authors: Pal
authors: Adam H
authors: AH
authors: Hart
authors: Marie-Liesse
authors: ML
authors: Asselin-Labat
authors: David E
authors: DE
authors: Gyorki
authors: Teresa
authors: T
authors: Ward
authors: Audrey
authors: A
authors: Partanen
authors: Frank
authors: F
authors: Feleppa
authors: Lily I
authors: LI
authors: Huschtscha
authors: Heather J
authors: HJ
authors: Thorne
authors: Stephen B
authors: SB
authors: Fox
authors: Max
authors: M
authors: Yan
authors: Juliet D
authors: JD
authors: French
authors: Melissa A
authors: MA
authors: Brown
authors: Gordon K
authors: GK
authors: Smyth
authors: Jane E
authors: JE
authors: Visvader
authors: Geoffrey J
authors: GJ
authors: Lindeman
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006579:Heterozygote; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009154:Mutation / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011980:Receptors, Progesterone / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D011980:Receptors, Progesterone