CD44 Expression in Intestinal Epithelium and Colorectal Cancer Is Independent of p53 Status |
| |
| Authors: | Jurrit Zeilstra Sander P. J. Joosten Louis Vermeulen Jan Koster Jan Paul Medema Rogier Versteeg Marcel Spaargaren Steven T. Pals |
| |
| Affiliation: | 1. Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; 2. Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; 3. Department of Oncogenomics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; National Cancer Centre, Singapore, |
| |
| Abstract: | CD44 marks stem cell-like cells in a number of tumour types, including colorectal cancer (CRC), while aberrant CD44 expression conveys increased tumourigenic, invasive, and metastatic potential. Previous data indicate that CD44 is a direct target of p53-mediated transcriptional repression in breast cancer. Since inactivating p53 mutations are frequent genetic events in CRC these could unleash expression of CD44. In the present study, we therefore explored the relation between p53 mutational status and CD44 expression in a cohort of 90 localized primary CRCs and studied the effect of radiation-induced p53 activation on CD44 expression. Interestingly, we observed that, in contrast to breast cancer, loss of function p53 mutations were not associated with elevated CD44 expression in colon cancer. Moreover, DNA-damage induced p53 activation did not result in repression of CD44 expression, neither in colon cancer cells nor in normal intestinal epithelial cells. Our data demonstrate that CD44 expression in normal and malignant intestinal epithelial cells is not regulated by p53, implying that regulation of this potentially important therapeutic target is tissue and cancer-type specific. |
| |
| Keywords: | |
|
|
