CD44 promotes resistance to apoptosis in murine colonic epithelium
Version of Record online: 16 DEC 2004
Copyright © 2004 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 203, Issue 3, pages 583–588, June 2005
How to Cite
Lakshman, M., Subramaniam, V., Wong, S. and Jothy, S. (2005), CD44 promotes resistance to apoptosis in murine colonic epithelium. J. Cell. Physiol., 203: 583–588. doi: 10.1002/jcp.20260
- Issue online: 24 MAR 2005
- Version of Record online: 16 DEC 2004
- Manuscript Accepted: 6 OCT 2004
- Manuscript Received: 8 SEP 2004
- Canadian Institutes of Health Research. Grant Number: MT-10315
Dysregulated expression of CD44 isoforms occurs consistently in colon carcinogenesis, and this change occurs also in most other types of cancer. One of the basic features of malignant transformation is the acquisition of resistance to apoptosis. We previously found that the colonic epithelium of mice, deficient in CD44 is predisposed to apoptosis. In this study, we asked whether the expression of CD44 alters the response of the colon to an apoptotic stimulus, and what are the mechanisms involved. For this, we assessed the susceptibility of the murine colon to apoptosis by total body irradiation to induce apoptosis. Apoptotic and concomitant changes relevant to the mechanisms of apoptosis were monitored by molecular markers of apoptosis. We found enhanced susceptibility to apoptosis in CD44 deficient colonic epithelium based on an increase in the number of apoptotic bodies, and activation of caspase 3. This was not associated with alterations in proliferations as shown by comparable Ki-67 expression and BrdU labeling. Furthermore, upregulated active caspase 3 in CD44 deficient colon was accompanied by concomitant molecular alterations in caspase 9 and not caspase 8, and this indicated the involvement of the mitochondrial pathway in apoptosis execution. Overall, this is the first report demonstrating CD44 mediated resistance to apoptosis in the colonic epithelium in vivo. This implicates CD44 in promoting cell transformation into a malignant phenotype, in conjunction with other anti-apoptotic factors. © 2004 Wiley-Liss, Inc.