Decreased expression of Mac-2 (carbohydrate binding protein 35) and loss of its nuclear localization are associated with the neoplastic progression of colon carcinoma
Department of Cancer Biology
Adenocarcinoma; Amino Acid Sequence; Antigens, Differentiation; Base Sequence; Blotting, Northern; Cell Nucleus; Cell Transformation, Neoplastic; Cloning, Molecular; Colon; Colonic Neoplasms; Colonic Polyps; DNA; DNA, Neoplasm; Galectin 3; Humans; Immunohistochemistry; Intestinal Mucosa; Lectins; Molecular Sequence Data; Molecular Weight; Oligodeoxyribonucleotides; Polymerase Chain Reaction; RNA; RNA, Messenger; RNA, Neoplasm
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.
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Citation: Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3466-70.