DOI: 10.1158/0008-5472.can-06-0054. Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells

Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells

10.1158/0008-5472.can-06-0054

Crossref journal-article

American Association for Cancer Research (AACR)

Cancer Research (1086)

Abstract

Abstract The epithelial components of the mammary gland are thought to arise from stem cells with a capacity for self-renewal and multilineage differentiation. Furthermore, these cells and/or their immediate progeny may be targets for transformation. We have used both in vitro cultivation and a xenograft mouse model to examine the role of hedgehog signaling and Bmi-1 in regulating self-renewal of normal and malignant human mammary stem cells. We show that hedgehog signaling components PTCH1, Gli1, and Gli2 are highly expressed in normal human mammary stem/progenitor cells cultured as mammospheres and that these genes are down-regulated when cells are induced to differentiate. Activation of hedgehog signaling increases mammosphere-initiating cell number and mammosphere size, whereas inhibition of the pathway results in a reduction of these effects. These effects are mediated by the polycomb gene Bmi-1. Overexpression of Gli2 in mammosphere-initiating cells results in the production of ductal hyperplasia, and modulation of Bmi-1 expression in mammosphere-initiating cells alters mammary development in a humanized nonobese diabetic-severe combined immunodeficient mouse model. Furthermore, we show that the hedgehog signaling pathway is activated in human breast “cancer stem cells” characterized as CD44+CD24−/lowLin−. These studies support a cancer stem cell model in which the hedgehog pathway and Bmi-1 play important roles in regulating self-renewal of normal and tumorigenic human mammary stem cells. (Cancer Res 2006; 66(12): 6063-71)

Bibliography

Liu, S., Dontu, G., Mantle, I. D., Patel, S., Ahn, N., Jackson, K. W., Suri, P., & Wicha, M. S. (2006). Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells. Cancer Research, 66(12), 6063â6071.

Authors 8

Suling Liu (first)
Gabriela Dontu (additional)
Ilia D. Mantle (additional)
Shivani Patel (additional)
Nam-shik Ahn (additional)
Kyle W. Jackson (additional)
Prerna Suri (additional)
Max S. Wicha (additional)

References 38 Referenced 953

Dates

Type	When
Created	19 years, 2 months ago (June 15, 2006, 5:49 p.m.)
Deposited	3 years, 2 months ago (June 16, 2022, 9:20 p.m.)
Indexed	6 days, 9 hours ago (Aug. 30, 2025, 12:40 p.m.)
Issued	19 years, 2 months ago (June 15, 2006)
Published	19 years, 2 months ago (June 15, 2006)
Published Online	19 years, 2 months ago (June 15, 2006)
Published Print	19 years, 2 months ago (June 15, 2006)

Funders 0

None

BibTeX

@article{Liu_2006, title={Hedgehog Signaling and Bmi-1 Regulate Self-renewal of Normal and Malignant Human Mammary Stem Cells}, volume={66}, ISSN={1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.can-06-0054}, DOI={10.1158/0008-5472.can-06-0054}, number={12}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Liu, Suling and Dontu, Gabriela and Mantle, Ilia D. and Patel, Shivani and Ahn, Nam-shik and Jackson, Kyle W. and Suri, Prerna and Wicha, Max S.}, year={2006}, month=jun, pages={6063–6071} }

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