Journal
CANCER LETTERS
Volume 223, Issue 1, Pages 159-167Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2004.10.013
Keywords
CEACAM; colorectal cancer; high mobility group-box; mesothelin/MPF; T-cell factor; Wnt pathway
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The colon cancer cell lines HT29 and SW480 were transfected with an N-terminal beta-catenin binding site-deficient high mobility group (HMG)-box T-cell factor I (Delta N-TCF-1) construct to identify differentially expressed genes. Oligonucleotide HG-U133A microarray expression profiling revealed increased mRNA levels of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 5, 6 and mesothelin in transfectants positive for nuclear Delta N-TCF-1B. Increased amounts of CEACAM5 (CEA) were detectable in membrane-associated compartments, particularly in cholesterol-enriched microdomains. Similarly, mesothelin was demonstrated as an uncleaved membrane-bound constituent. The identified markers were examined in specimens of 46 colorectal carcinomas (CRC) by immunohistochemistry. Patchy areas of increased CEACAM5/6 staining were seen at the tumour-host front in all samples studied. Twenty-eight (58%) of these cases showed over-expression of mesothelin in a small fraction of tumor cells displaying dedifferentiation and dissemination at the invasion front. We conclude that forced expression of Delta N-TCF-1B in HT29 and SW480 is associated with up-regulation of GPI-anchored adhesion molecules, which were assigned to the tumour-host front in CRC patients. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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