New evidence for an extra-hepatic role of N- acetylglucosaminyltransferase III in the progression of diethylnitrosamine- induced liver tumors in mice

Xiaoping Yang, Mantu Bhaumik, Riddhi Bhattacharyya, Shih Gong, Charles E. Rogler, Pamela Stanley

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

N-acetylglucosaminyltransferase III (GlcNAc-TIII) is encoded by the Mgat3 gene and catalyzes the addition of the bisecting GlcNAc to the core of N-glycans. Mice lacking GlcNAc-TIII due to the insertion mutation Mgat3(tmlPst) (termed Mgat3(neo), exhibit retarded progression of liver tumors induced by diethylnitrosamine (DEN; M. Bhaumik et al., Cancer Res., 58: 2881-2887, 1998). This phenotype seemed to be due to a reduction, in activity or amount, of a circulating glycoprotein(s) that enhances DEN- induced liver tumor progression. Here, we provide new evidence to support this hypothesis. First, we show that mice with a deletion mutation of the Mgat3 gene coding exon (Mgat3(tmlJxm), termed Mgat3(Δ)) also exhibit retarded progression of DEN-induced liver tumors. At 7 months there was a significant decrease in liver weight (~27%; P < 0.01), reflecting reduced tumor burden in Mgat3(Δ/ζD) mice. In addition, tumors were generally fewer and smaller, and histological changes were less severe in Mgat3(Δ/Δ) livers. Therefore, tumor progression is retarded in mice with two different null mutations in the Mgat3 gene. Second, we show that the development of DEN-induced tumors is unaltered by high levels of GlcNAc-TIII in the liver of transgenic mice. The Mgat3 gene coding exon under the control of the major urinary protein (MUP) promoter was used to generate transgenic mice that express GlcNAc-TIII in liver. Following DEN injection and phenobarbitol treatment, however, no significant differences were observed between MUP/Mgat3 transgenic and control mice in either tumor numbers or liver weight. The combined data provide strong evidence that retarded progression of tumors in mice lacking GlcNAc-TIII is due to the absence of the bisecting GlcNAc residue on N-glycans of a circulating glycoprotein(s) from a tissue other than liver.

Original languageEnglish (US)
Pages (from-to)3313-3319
Number of pages7
JournalCancer Research
Volume60
Issue number12
StatePublished - Jun 15 2000

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beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase
Diethylnitrosamine
Liver
Neoplasms
Transgenic Mice
Genes
Polysaccharides
Exons
Glycoproteins
Weights and Measures
Sequence Deletion
Insertional Mutagenesis
Tumor Burden

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

New evidence for an extra-hepatic role of N- acetylglucosaminyltransferase III in the progression of diethylnitrosamine- induced liver tumors in mice. / Yang, Xiaoping; Bhaumik, Mantu; Bhattacharyya, Riddhi; Gong, Shih; Rogler, Charles E.; Stanley, Pamela.

In: Cancer Research, Vol. 60, No. 12, 15.06.2000, p. 3313-3319.

Research output: Contribution to journalArticle

Yang, Xiaoping ; Bhaumik, Mantu ; Bhattacharyya, Riddhi ; Gong, Shih ; Rogler, Charles E. ; Stanley, Pamela. / New evidence for an extra-hepatic role of N- acetylglucosaminyltransferase III in the progression of diethylnitrosamine- induced liver tumors in mice. In: Cancer Research. 2000 ; Vol. 60, No. 12. pp. 3313-3319.
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abstract = "N-acetylglucosaminyltransferase III (GlcNAc-TIII) is encoded by the Mgat3 gene and catalyzes the addition of the bisecting GlcNAc to the core of N-glycans. Mice lacking GlcNAc-TIII due to the insertion mutation Mgat3(tmlPst) (termed Mgat3(neo), exhibit retarded progression of liver tumors induced by diethylnitrosamine (DEN; M. Bhaumik et al., Cancer Res., 58: 2881-2887, 1998). This phenotype seemed to be due to a reduction, in activity or amount, of a circulating glycoprotein(s) that enhances DEN- induced liver tumor progression. Here, we provide new evidence to support this hypothesis. First, we show that mice with a deletion mutation of the Mgat3 gene coding exon (Mgat3(tmlJxm), termed Mgat3(Δ)) also exhibit retarded progression of DEN-induced liver tumors. At 7 months there was a significant decrease in liver weight (~27{\%}; P < 0.01), reflecting reduced tumor burden in Mgat3(Δ/ζD) mice. In addition, tumors were generally fewer and smaller, and histological changes were less severe in Mgat3(Δ/Δ) livers. Therefore, tumor progression is retarded in mice with two different null mutations in the Mgat3 gene. Second, we show that the development of DEN-induced tumors is unaltered by high levels of GlcNAc-TIII in the liver of transgenic mice. The Mgat3 gene coding exon under the control of the major urinary protein (MUP) promoter was used to generate transgenic mice that express GlcNAc-TIII in liver. Following DEN injection and phenobarbitol treatment, however, no significant differences were observed between MUP/Mgat3 transgenic and control mice in either tumor numbers or liver weight. The combined data provide strong evidence that retarded progression of tumors in mice lacking GlcNAc-TIII is due to the absence of the bisecting GlcNAc residue on N-glycans of a circulating glycoprotein(s) from a tissue other than liver.",
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AU - Stanley, Pamela

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