Wnt/β-catenin mediates radiation resistance of Sca1+ progenitors in an immortalized mammary gland cell line
Author:
Chen Mercy S.1, Woodward Wendy A.2, Behbod Fariba1, Peddibhotla Sirisha1, Alfaro Maria P.1, Buchholz Thomas A.2, Rosen Jeffrey M.1
Affiliation:
1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, M638a Houston, TX 77030-3498, USA 2. Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
Abstract
The COMMA-Dβ-geo cell line has been shown to contain a permanent subpopulation of progenitor cells that are enriched in outgrowth potential. Using the COMMA-Dβ-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-Dβ-geo murine mammary cell line. At a clinically relevant dose, the Sca1+ cells were resistant to radiation (2 Gy). Sca1+ cells contained fewer γ-H2AX+ DNA damage foci following irradiation, displayed higher levels of endogenous β-catenin, and selectively upregulated survivin after radiation. Expression of active β-catenin enhanced self-renewal preferentially in the Sca1+ cells, whereas suppressing β-catenin with a dominant negative, β-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-Dβ-geo cell line may provide a useful model to study the signaling pathways that control mammary progenitor cell regulation.
Publisher
The Company of Biologists
Reference57 articles.
1. Arai, F., Hirao, A., Ohmura, M., Sato, H., Matsuoka, S., Takubo, K., Ito, K., Koh, G. Y. and Suda, T. (2004). Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. Cell118, 149-161. 2. Ayyanan, A., Civenni, G., Ciarloni, L., Morel, C., Mueller, N., Lefort, K., Mandinova, A., Raffoul, W., Fiche, M., Dotto, G. P. et al. (2006). Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism. Proc. Natl. Acad. Sci. USA103, 3799-3804. 3. Bao, S., Wu, Q., McLendon, R. E., Hao, Y., Shi, Q., Hjelmeland, A. B., Dewhirst, M. W., Bigner, D. D. and Rich, J. N. (2006). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature444, 756-760. 4. Brabletz, T., Hlubek, F., Spaderna, S., Schmalhofer, O., Hiendlmeyer, E., Jung, A. and Kirchner, T. (2005). Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs179, 56-65. 5. Clarke, M. F. and Fuller, M. (2006). Stem cells and cancer: two faces of eve. Cell124, 1111-1115.
Cited by
150 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献
|
|