Mapping of two new epitopes on the apomucin encoded by MUC5AC gene: expression in normal GI tract and colon tumors.
Three hybridomas secreting monoclonal antibodies (MAbs) against human (62M MAb) or rat (463M and 589M MAbs) gastric mucins were isolated. These MAbs immunoreacted against a human recombinant protein encoded by the 3' region of the MUC5AC gene. We have mapped 2 new gastric mucin epitopes and the M1-f epitope previously characterized by the 19/21M1 MAbs on MUC5AC-encoded apomucin. The M1-f, 463/589M and 62M epitopes are located in the MUC11p15/von Willebrand factor (vWF)-A3uD4 domain, in the D4-(vWF)-like domain and in the C- and CK-vWF-like domains of MUC5AC, respectively. The 463/589M and 62M MAbs stained the surface epithelium of human gastric mucosae, but not the normal colon mucosae (except 463/589M MAbs, which immunoreacted with 5 of 49 cases). All hyperplastic polyps are stained strongly with the 463/589M MAbs and faintly with the 62M MAb. In addition, 463/589M epitope was detected in 64% of the adenomas and in 93% of the mucosae adjacent to adenocarcinomas; in contrast, only 9% of the adenomas and 29% of the mucosae adjacent to adenocarcinomas expressed the 62M epitope. The expression pattern of the 463/589M epitope in colonic carcinogenesis is different from that of the 19/21M1 epitope, although the 2 epitopes are encoded by MUC5AC gene.
Nollet
Séverine
S
INSERM U-482, Hôpital Saint-Antoine, Paris, France.
Forgue-Lafitte
Marie-Elisabeth
ME
Kirkham
Paul
P
Bara
Jacques
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004064:Digestive System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry; D005752:Gastric Mucins / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC; D009077:Mucins / Q000737:chemistry*; D009092:Mucous Membrane / Q000378:metabolism; D010449:Peptide Mapping; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D000939:Epitopes; D005752:Gastric Mucins; C524678:MUC5AC protein, human; C524679:Muc5ac protein, mouse; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D010455:Peptides; C053366:apomucin