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JCS ePress online publication date 16 Jan 2007
doi: 10.1242/jcs.03348

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Research Article

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


Mercy S. Chen, Wendy A. Woodward, Fariba Behbod, Sirisha Peddibhotla, Maria P. Alfaro, Thomas A. Buchholz, and Jeffrey M. Rosen*
* Author for correspondence (e-mail: jrosen{at}bcm.edu)

The COMMA-D{beta}-geo cell line has been shown to contain a permanent subpopulation of progenitor cells that are enriched in outgrowth potential. Using the COMMA-D{beta}-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{beta}-geo murine mammary cell line. At a clinically relevant dose, the Sca1+ cells were resistant to radiation (2 Gy). Sca1+ cells contained fewer {gamma}-H2AX+ DNA damage foci following irradiation, displayed higher levels of endogenous {beta}-catenin, and selectively upregulated survivin after radiation. Expression of active {beta}-catenin enhanced self-renewal preferentially in the Sca1+ cells, whereas suppressing {beta}-catenin with a dominant negative, {beta}-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{beta}-geo cell line may provide a useful model to study the signaling pathways that control mammary progenitor cell regulation.


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