Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line.
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.
Chen
Mercy S
MS
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, M638a Houston, TX 77030-3498, USA.
Woodward
Wendy A
WA
Behbod
Fariba
F
Peddibhotla
Sirisha
S
Alfaro
Maria P
MP
Buchholz
Thomas A
TA
Rosen
Jeffrey M
JM
D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000528:radiation effects; D011836:Radiation Tolerance / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D051153:Wnt Proteins; D051176:beta Catenin