title: Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, M638a Houston, TX 77030-3498, USA.
authors.forename: Mercy S
authors.initials: MS
authors.lastname: Chen
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.forename: Fariba
authors.initials: F
authors.lastname: Behbod
authors.forename: Sirisha
authors.initials: S
authors.lastname: Peddibhotla
authors.forename: Maria P
authors.initials: MP
authors.lastname: Alfaro
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rosen
mesh_terms: 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*
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin