First Author | Chen MS | Year | 2007 |
Journal | J Cell Sci | Volume | 120 |
Issue | Pt 3 | Pages | 468-77 |
PubMed ID | 17227796 | Mgi Jnum | J:120774 |
Mgi Id | MGI:3707949 | Doi | 10.1242/jcs.03348 |
Citation | Chen MS, et al. (2007) Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line. J Cell Sci 120(Pt 3):468-77 |
abstractText | The COMMA-Dbeta-geo cell line has been shown to contain a permanent subpopulation of progenitor cells that are enriched in outgrowth potential. Using the COMMA-Dbeta-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-Dbeta-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-Dbeta-geo cell line may provide a useful model to study the signaling pathways that control mammary progenitor cell regulation. |