Differential CD74 (major histocompatibility complex Class II invariant chain) expression in mouse and human intestinal adenomas.
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.
Cuthbert
R J
RJ
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.
Wilson
J M
JM
Scott
N
N
Coletta
P L
PL
Hull
M A
MA
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
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