Colon cancer tissues display an increased activity of
beta-galactoside alpha2,6 sialyltransferase (
ST6Gal.I) and an increased reactivity with the
lectin from Sambucus nigra (SNA), specific for alpha2,6-sialyl-linkages. Experimental and clinical studies indicate a contribution of these alterations to
tumor progression, but their molecular bases are largely unknown. In many tissues,
ST6Gal.I is transcriptionally regulated through the usage of different promoters that originate mRNAs diverging in the
5;-untranslated regions. RT-PCR analysis of 14
carcinoma samples, all expressing an increased
ST6Gal.I enzyme activity, and of the corresponding normal mucosa revealed the presence of at least 2 transcripts. One, containing the 5;-untranslated exons, Y+Z, is thought to represent the "housekeeping" expression, and another previously described in hepatic tissues. Both the Y+Z and the hepatic transcripts were detectable in normal and
cancer tissues but that latter form had a marked tendency to accumulate in
cancer. The extent of alpha2,6-sialylation of
glycoconjugates, as determined by SNA-dot blot analysis, was markedly enhanced in all
cancer specimens, but the level of reactivity only partially correlated with the level of
enzyme expression. Western blot analysis revealed a strikingly heterogeneous pattern of SNA reactivity among
cancer tissues. These data indicate that: i) during neoplastic transformation of colonic cells,
ST6Gal.I expression may be modulated through a differential promoter usage; ii) the extent of alpha2,6-sialylation of
cancer cell membranes is not a direct function of the
ST6Gal.I activity, strongly suggesting the existence of other, more complex mechanisms of regulation.