CD44 expression in intestinal epithelium and colorectal cancer is independent of p53 status

PLoS One. 2013 Aug 29;8(8):e72849. doi: 10.1371/journal.pone.0072849. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Female
  • Gene Expression Regulation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyaluronan Receptors / genetics*
  • Hyaluronan Receptors / metabolism
  • Intestinal Mucosa / metabolism*
  • Male
  • Mice
  • Middle Aged
  • Mutation
  • Protein Binding
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Hyaluronan Receptors
  • Tumor Suppressor Protein p53

Grant support

This work has been funded by the Dutch Cancer Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.