40 Citations (Scopus)

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

Fingerprint

Telomerase
Breast
Stem Cells
Integrin alpha6beta1
Breast Neoplasms
Neoplastic Stem Cells
Vimentin
Cadherins
Microarray Analysis
Neoplasms
Epithelial Cells

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate. / Zhao, Xiangshan; Malhotra, Gautam K.; Lele, Subodh M; Lele, Manjiri S.; West, William W.; Eudy, James D; Band, Hamid; Band, Vimla.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 32, 10.08.2010, p. 14146-14151.

Research output: Contribution to journalArticle

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title = "Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate",
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.",
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author = "Xiangshan Zhao and Malhotra, {Gautam K.} and Lele, {Subodh M} and Lele, {Manjiri S.} and West, {William W.} and Eudy, {James D} and Hamid Band and Vimla Band",
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T1 - Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate

AU - Zhao, Xiangshan

AU - Malhotra, Gautam K.

AU - Lele, Subodh M

AU - Lele, Manjiri S.

AU - West, William W.

AU - Eudy, James D

AU - Band, Hamid

AU - Band, Vimla

PY - 2010/8/10

Y1 - 2010/8/10

N2 - 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.

AB - 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.

KW - Immortalization

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KW - Mammary epithelial cells

KW - Selfrenewal

KW - Stem cell

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