Journal article

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

Peter Eirew, Nagarajan Kannan, David JHF Knapp, Francois Vaillant, Joanne T Emerman, Geoffrey J Lindeman, Jane E Visvader, Connie J Eaves



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..

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Awarded by Canadian Breast Cancer Research Alliance

Awarded by U.S. Department of Defense Breast Cancer

Awarded by National Health and Medical Research Council (Australia)

Funding Acknowledgements

We acknowledge the excellent technical contributions of D. Wilkinson, G. Edin, and the staff of the Flow Cytometry Facilities of the Terry Fox Laboratory and the Walter and Eliza Hall Institute. Mammoplasty tissue, generously donated by patients, was obtained with the assistance of Drs. J. Sproul, P. Lennox, N. Van Laeken, and R. Warren (Canada) and the Victorian Cancer Bio-bank (Australia). This work was supported by the Canadian Breast Cancer Research Alliance (Grant CBCRA 019343), the U.S. Department of Defense Breast Cancer Research Program (Predoctoral Fellowship number W81XWH-06-1-0702), the Canadian Breast Cancer Foundation BC/Yukon (Fellowship to N. Kannan), the National Health and Medical Research Council (Australia, Grants #461224 and #461221), the Victorian Government through the Victorian Cancer Agency/Victorian Breast Cancer Research Consortium and an Operational Infrastructure Support grant, and the Australian Cancer Research Foundation.