Abstract

There is increasing evidence that breast and other cancers originate from and are maintained by a small fraction of stem/progenitor cells with self-renewal properties. Whether such cancer stem/progenitor cells originate fromnormal stemcells based on initiation of a de novo stem cell program, by reprogramming of a more differentiated cell type byoncogenic insults, orbothremainsunresolved.Amajorhurdle in addressing these issues is lack of immortal human stem/progenitor cells that can be deliberately manipulated in vitro. We present evidence that normal and human telomerase reverse transcriptase (hTERT)-immortalized human mammary epithelial cells (hMECs) isolated and maintained in Dana-Farber Cancer Institute 1 (DFCI-1) medium retain a fraction with progenitor cell properties. These cells coexpress basal (K5, K14, and vimentin), luminal (E-cadherin, K8, K18, or K19), and stem/progenitor (CD49f, CD29, CD44, and p63) cell markers. Clonal derivatives of progenitors coexpressing these markers fall into two distinct types - a K5 +/K19- type and a K5+/K19+ type. We show that both types of progenitor cells have self-renewal and differentiation ability. Microarray analyses confirmed the differential expression of components of stem/progenitor-associated pathways, such as Notch, Wnt, Hedgehog, and LIF, in progenitor cells compared with differentiated cells. Given the emerging evidence that stem/progenitor cells serve as precursors for cancers, these cellular reagents represent a timely and invaluable resource to explore unresolved questions related to stem/progenitor origin of breast cancer.

Original languageEnglish (US)
Pages (from-to)14146-14151
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number32
DOIs
StatePublished - Aug 10 2010

Keywords

  • Immortalization
  • In vitro stem cell model
  • Mammary epithelial cells
  • Selfrenewal
  • Stem cell

ASJC Scopus subject areas

  • General

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