The c-Ha-ras oncogene induces increased expression of β-galactoside α-2,6-sialyltransferase in rat fibroblast (FR3T3) cells

Abstract

Alteration in cell surface carbohydrates, and in particular cell surface sialylation, have been known to occur during oncogenic transformation. To examine the basis for such changes, we have transformed the rat fibroblast cell line FR3T3 with the oncogenes c-Ha-ras EJ, v-mycOK10, v-src, polyoma virus middle T or the transforming bovine papilloma virus 1 (BPV1), and measured the sialytransferase activities of cellular lysates. We found that, in contrast to all other oncogenes examined, c-Ha-ras induced a striking increase in beta-galactoside alpha-2,6-sialytransferase (Gal alpha-2,6-ST) activity in FR3T3 cells. This increase in Gal alpha-2,6-ST activity resulted in the increased expression of cell surface alpha-2,6-linked sialic acid on cell surface glycoconjugates, as determined by cell staining with fluorescein-labelled Sambucus nigra agglutinin. Immunoprecipitation and immunofluorescence experiments revealed that the increase in Gal alpha-2,6-ST activity was due to an elevation of expression of the enzyme. Moreover, Northern analysis suggested that the increased expression of this enzyme was the result of an increase in the steady-state mRNA level of the Gal alpha-2,6-ST gene. These results support the notion that alterations seen in cell surface glycoconjugates during oncogenic transformation can be the result of altered expression of glycosyltransferases.

An Oncogenic Protein Golgi Phosphoprotein 3 Up-regulates Cell Migration via Sialylation

“…Indeed, elevated levels of ST6GAL1 and ␣2,6-sialylation have been observed in several types of tumors, including colon cancer (18,52) and ovarian cancer (42,53). The expression levels of ST6GAL1 mRNA and enzyme activities are known to be particularly enhanced in metastatic tumors, which were promoted by the Ras oncogene (15,16). Consistently, in vitro cell culture studies have suggested that ST6GAL1 up-regulation contributes to cancer metastasis by regulating invasiveness and/or cell motility (18,54), as observed in this study.…”

“…Increased expression has been reported in carcinomas of the colon (11), breast (12), cervix (13), and ovary (9) and in some brain tumors (14). The expression level of the ␣2,6-sialyltransferase-I (ST6GAL1) gene is up-regulated by the Ras oncogene (15,16). However, the molecular mechanism for the post-translational regulation of sialylations in cancer cells remains unclear.…”

The (1→6)-β-Glucan Moiety Represents a Cross-Reactive Epitope of Infection-Induced Malignancy Surveillance

“…Alteration in glycosylation in cancer cells often reflects a deregulation of glycosyl transferase expression at the transcription level. For instance, glycosyltransferase genes (e.g., ST6GAL1 and MGAT5) are regulated by oncogenes (35,36). Identification of additional glycoproteins carrying the (1→6)- b-glucan cross-reactive glycotope may provide useful clues to these questions.…”

The her-2/neu oncogene stimulates the transcription of N-acetylglucosaminyltransferase V and expression of its cell surface oligosaccharide products

“…A common alteration involves the increase in particular N-linked oligosaccharides when cells are transformed by a number of tumor viruses, including Rous sarcoma virus and polyoma virus, and oncogenes such as ras and fps/yes (Buck et al, 1971;Le Marer et al, 1992;Lu and Chaney, 1993;Pierce and Arango, 1986;Yamashita et al, 1984). These oligosaccharides contain a b(1,6) branched N-acetylglucosamine (GlcNAc) and their synthesis is catalyzed by the glycosyltransferase, N -acetylglucosaminyltransferase V (E. C. 2.…”