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First published online 16 January 2007
doi: 10.1242/jcs.03348

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Wnt/-catenin mediates radiation resistance of Sca1⁺ progenitors in an immortalized mammary gland cell line

Mercy S. Chen^1,*, Wendy A. Woodward^2,*, Fariba Behbod¹, Sirisha Peddibhotla¹, Maria P. Alfaro¹, Thomas A. Buchholz² and Jeffrey M. Rosen^1,

¹ Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, M638a Houston, TX 77030-3498, USA
² Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

Author for correspondence (e-mail: jrosen{at}bcm.edu)

Accepted 15 November 2006

The COMMA-D-geo cell line has been shown to contain a permanent subpopulation of progenitor cells that are enriched in outgrowth potential. Using the COMMA-D-geo cell line as a model, we sought to study the radioresistance of mammary progenitor cells. Using the putative progenitor cell marker stem cell antigen 1 (Sca1), we were able to isolate a discrete subpopulation of Sca1⁺ multipotent cells from the immortalized COMMA-D-geo murine mammary cell line. At a clinically relevant dose, the Sca1⁺ cells were resistant to radiation (2 Gy). Sca1⁺ cells contained fewer -H2AX⁺ DNA damage foci following irradiation, displayed higher levels of endogenous -catenin, and selectively upregulated survivin after radiation. Expression of active -catenin enhanced self-renewal preferentially in the Sca1⁺ cells, whereas suppressing -catenin with a dominant negative, -engrailed, decreased self-renewal of the Sca1⁺ cells. Understanding the radioresistance of progenitor cells may be an important factor in improving the treatment of cancer. The COMMA-D-geo cell line may provide a useful model to study the signaling pathways that control mammary progenitor cell regulation.

Key words: -catenin, Mammary gland, Stem, Progenitor, Cell line, COMMA-D, -geo, Sca1

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