Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2123679 | European Journal of Cancer | 2009 | 10 Pages |
Abstract
CD74 (major histocompatibility complex (MHC) Class II invariant chain) has recently been identified as the cell-surface receptor for the pro-tumorigenic cytokine macrophage migration inhibitory factor (MIF). Therefore, we investigated CD74 gene expression in intestinal adenomas in ApcMin/+ mice and humans. CD74 mRNA (p31 and p41 splice variants) and immunoreactive CD74 protein levels were significantly lower in small intestinal and colonic ApcMin/+ mouse adenomas compared with histologically normal mucosa. These findings were mirrored by a reduction in MHC Class II expression and Class II trans-activator type IV transcripts. Conversely, CD74 protein levels were actually increased in dysplastic epithelial cells in 47/55 (85%) human colorectal adenomas, with CD74 and MIF protein levels together predicting increasing dysplasia in individual adenomas (PÂ =Â 0.003). Down-regulation of CD74 during ApcMin/+ mouse intestinal tumorigenesis does not model increased CD74 expression at the early, benign stages of human colorectal carcinogenesis. Epithelial cell CD74 represents a valid target for anti-CRC therapy.
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Authors
R.J. Cuthbert, J.M. Wilson, N. Scott, P.L. Coletta, M.A. Hull,