title: CD44 expression in intestinal epithelium and colorectal cancer is independent of p53 status.
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.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Jurrit
authors.initials: J
authors.lastname: Zeilstra
authors.forename: Sander P J
authors.initials: SP
authors.lastname: Joosten
authors.forename: Louis
authors.initials: L
authors.lastname: Vermeulen
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Medema
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
authors.forename: Marcel
authors.initials: M
authors.lastname: Spaargaren
authors.forename: Steven T
authors.initials: ST
authors.lastname: Pals
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D018960:Hyaluronan Receptors; D016159:Tumor Suppressor Protein p53