Unusually high expression of N-Acetylglucosaminyltransferase-IVa in human choriocarcinoma cell lines: A possible enzymatic basis of the formation of abnormal biantennary sugar chain

Structural analysis of the sugar chains of human chorionic gonadotropin (hC G) has revealed that abnormal biantennary structures appear specifically on hCG in the urine of choriocarcinoma patients. However, the enzymatic and m olecular mechanisms of the biosynthesis of abnormal biantennary sugar chain s have not yet been elucidated. In this report, the enzyme activities and t he expression levels of mRNAs of N-acetylglucosaminyltransferases (GnT)-I t o -V, beta-1,4-galactosyltransferase, and alpha-mannosidase LI in normal hu man placentae and three human choriocarcinoma cell Lines were investigated, GnT-IV activities in choriocarcinoma cell lines were increased from 16- to 66-fold and GnT-III activity was increased from 15- to 25-fold as compared with those in human placentae, whereas other enzyme activities were not in creased significantly. The mRNA expression levels generally correlated with their enzyme activities, Among the two GnT-IV genes found in human tissues only GnT-IVa gene was strongly expressed in the cancer cells: from three t o seven times as much as in the normal tissue, whereas that of GnT-IVb rema ined constant, On the basis of these results, we proposed that ectopic expr ession of GnT-IVa gene should occur along with the malignancy of trophoblas tic tissues, and that the increased GnT-IV activity should be the main caus e of the formation of abnormal biantennary sugar chains in choriocarcinoma, A possible enzymatic basis of the biosynthesis of abnormal biantennary sug ar chains is discussed.