Abstract
The Mac-2 lectin (carbohydrate binding protein 35) is a soluble, 32- to 35-kDa phosphoprotein that binds galactose-containing glycoconjugates. We report here that the colonic epithelium is a major site of Mac-2 expression in vivo based on immunohistochemistry of human tissue specimens. In this epithelium, proliferating cells at the base of the crypts do not express Mac-2 but its expression increases with differentiation along the crypt-to-surface axis. Mac-2 expression is concentrated in the nuclei of these differentiated epithelial cells. The progression from normal mucosa to adenoma to carcinoma is associated with significant changes in Mac-2 nuclear localization and expression. In all adenomas (9/9) and carcinomas (13/13) examined, Mac-2 was not present in the nucleus but was localized in the cytoplasm. Sequencing of Mac-2 cDNAs from normal mucosa and carcinoma revealed no specific mutations that could account for this loss of nuclear localization. We also observed a 5- to 10-fold decrease in Mac-2 mRNA levels in cancer compared to normal mucosa as well as a significant reduction in the amount of Mac-2 protein expressed. These observations suggest that Mac-2 exclusion from the nucleus and its decreased expression may be related to the neoplastic progression of colon cancer.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology
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Amino Acid Sequence
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / genetics
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Antigens, Differentiation / metabolism*
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Base Sequence
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Blotting, Northern
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Cell Nucleus / metabolism
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Cell Nucleus / ultrastructure*
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Cell Transformation, Neoplastic
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Cloning, Molecular
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Colon / cytology
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Colon / metabolism*
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Colon / pathology
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / pathology
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Colonic Polyps / metabolism*
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Colonic Polyps / pathology
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DNA / genetics
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DNA / isolation & purification
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DNA, Neoplasm / genetics
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DNA, Neoplasm / isolation & purification
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Galectin 3
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Humans
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Immunohistochemistry
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Intestinal Mucosa / cytology
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Intestinal Mucosa / metabolism*
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Intestinal Mucosa / pathology
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Lectins / biosynthesis
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Lectins / genetics
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Lectins / metabolism*
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Molecular Sequence Data
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Molecular Weight
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Oligodeoxyribonucleotides
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Polymerase Chain Reaction / methods
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RNA / genetics
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RNA / isolation & purification
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RNA, Messenger / genetics
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RNA, Messenger / isolation & purification
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RNA, Messenger / metabolism
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RNA, Neoplasm / genetics
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RNA, Neoplasm / isolation & purification
Substances
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Antigens, Differentiation
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DNA, Neoplasm
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Galectin 3
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Lectins
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Oligodeoxyribonucleotides
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RNA, Messenger
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RNA, Neoplasm
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RNA
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DNA