title: Differential CD74 (major histocompatibility complex Class II invariant chain) expression in mouse and human intestinal adenomas.
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 Apc(Min/+) mice and humans. CD74 mRNA (p31 and p41 splice variants) and immunoreactive CD74 protein levels were significantly lower in small intestinal and colonic Apc(Min/+) 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 (P=0.003). Down-regulation of CD74 during Apc(Min/+) 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.
authors.affiliation: Section of Molecular Gastroenterology, Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Cuthbert
authors.forename: J M
authors.initials: JM
authors.lastname: Wilson
authors.forename: N
authors.initials: N
authors.lastname: Scott
authors.forename: P L
authors.initials: PL
authors.lastname: Coletta
authors.forename: M A
authors.initials: MA
authors.lastname: Hull
mesh_terms: D000236:Adenoma / Q000276:immunology*; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015534:Trans-Activators; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human