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

J Cell Sci. 2007 Feb 1;120(Pt 3):468-77. doi: 10.1242/jcs.03348. Epub 2007 Jan 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic
  • Female
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Animal / radiation effects*
  • Mice
  • Mice, Inbred BALB C
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / radiation effects
  • Radiation Tolerance / physiology*
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*


  • Wnt Proteins
  • beta Catenin