Expression of N-acetyllactosamine and β1,4-Galactosyltransferase (β4GalT-I) During Adenoma-Carcinoma Sequence in the Human Colorectum

Abstract

SUMMARYWe set out to determine the expression profiles of glycoproteins possessing N-acetyllactosamine, a precursor carbohydrate of sialyl Le x , during colorectal cancer development. We immunohistochemically analyzed the distribution of N-acetyllactosamine as well as of ␤4GalT-I, a member of the ␤1,4-galactosyltransferase family responsible for N-acetyllactosamine biosynthesis, in normal mucosa and in adenoma and carcinoma of the human colorectum. Using monoclonal antibody H11, N-acetyllactosamine was barely detectable in the normal mucosa. In low-grade adenoma, however, N-acetyllactosamine was weakly but definitely expressed on the cell surface, and its expression level was moderately increased in high-grade adenoma and markedly increased in carcinoma in situ as well as in advanced carcinoma. To detect ␤4GalT-I, we used a newly developed polyclonal antibody (designated A18G), which is specific for the stem region of human ␤4GalT-I. Faint expression of ␤4GalT-I was detectable in normal mucosa, and the expression level was moderately increased in low-grade adenoma and in high-grade adenoma and markedly increased in carcinoma in situ and advanced carcinoma. The expression of N-acetyllactosamine was highly correlated with the expression of ␤4GalT-I in these tumor cells. These results indicate that the expression level of ␤4GalT-I is apparently enhanced during tumorigenesis in the colorectum and that ␤4GalT-I mostly directs the carcinoma-associated expression of N-acetyllactosamine on the colorectal tumor cell surface. (J Histochem Cytochem 47:1593-1601, 1999)

Lewis Type 1 Antigen Synthase (β3Gal-T5) Is Transcriptionally Regulated by Homeoproteins

“…Thus, it is speculated that down-regulation of ␤3Gal-T5 expression in cancer cells might cause the alteration of carbohydrate structures, for example, an extension of the polylactosamine chain or conversion from type 1 to type 2. In fact, the N-acetyllactosamine structure was significantly increased in colon cancer (37,38). Although Ichikawa et al (38) concluded that an increase of ␤4Gal-TI in cancer cells was responsible for such alterations, the ␤4Gal-T activity in cancerous tissue was reported to be essentially unchanged (7).…”

“…In fact, the N-acetyllactosamine structure was significantly increased in colon cancer (37,38). Although Ichikawa et al (38) concluded that an increase of ␤4Gal-TI in cancer cells was responsible for such alterations, the ␤4Gal-T activity in cancerous tissue was reported to be essentially unchanged (7).…”

Immunohistochemical demonstration of apoptosis-regulated proteins, Bcl-2 and Bax, in resected non-small-cell lung cancers

“…IHC results were assessed according to a scoring system based on the criteria of Ichikawa et al 6 as follows. The staining intensity ranged from 0 to 3 (0, absent; 1, weak; 2, moderate; 3, strong).…”

Specificity of β1,4-galactosyltransferase inhibition by 2-naphthyl 2-butanamido-2-deoxy-1-thio-β-D-glucopyranoside

“…The activity and transcript levels of β3GalT5 were shown to be decreased in tissue samples of human colon adenocarcinoma, relative to the surrounding normal mucosa [15][16][17]. In contrast, the activity of β4GalT has been found to be increased in cancer [21][22][23]. The activity or mRNA levels of β4GalT also increase in endothelial and cartilage derived cells after treatment of cells with tumor necrosis factor (TNF)α [24,25].…”