Aldehyde Dehydrogenase Activity Is a Biomarker of Primitive Normal Human Mammary Luminal Cells§

Authors

  • Peter Eirew,

    1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
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  • Nagarajan Kannan,

    1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
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  • David J.H.F. Knapp,

    1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
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  • François Vaillant,

    1. Breast Cancer Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    2. Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
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  • Joanne T. Emerman,

    1. Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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  • Geoffrey J. Lindeman,

    1. Breast Cancer Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    2. Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
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  • Jane E. Visvader,

    1. Breast Cancer Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    2. Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
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  • Connie J. Eaves

    Corresponding author
    1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    2. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
    • Terry Fox Laboratory, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada
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    • Telephone: 604-675-8122; Fax: 604-877-0712


  • Author contributions: P.E.: conception and design, collection of data, data analysis and interpretation, and manuscript writing; N.K. and F.V.: collection of data and data analysis and interpretation; D.J.H.F.K.: data analysis and interpretation; G.J.L. and J.E.V.: conception and design and manuscript writing; J.T.E.: provision of study material; C.J.E.: conception and design, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS November 30, 2011.

Abstract

Elevated aldehyde dehydrogenase (ALDH) expression/activity has been identified as an important biomarker of primitive cells in various normal and malignant human tissues. Here we examined the level and type of ALDH expression and activity in different subsets of phenotypically and functionally defined normal human mammary cells. We find that the most primitive human mammary stem and progenitor cell types with bilineage differentiation potential show low ALDH activity but undergo a marked, selective, and transient upregulation of ALDH activity at the point of commitment to the luminal lineage. This mirrors a corresponding change in transcripts and protein levels of ALDH1A3, an enzyme involved in retinoic acid synthesis and the most highly expressed ALDH gene in normal human mammary tissue. In contrast, ALDH1A1 is expressed at low levels in all mammary epithelial cells. These findings raise interesting questions about the reported association of ALDH activity with breast cancer stem cells and breast cancer prognosis. STEM CELLS 2012; 30:344–348.

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