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Reduced trisialoganglioside synthesis in chemically but not mos-transformed mouse epidermal cells
Abstract:
A specific decrease in the net de novo synthesis ([1-14C]-glucosamine incorporation) of cell surface trisialoganglioside (GT) occurs in preneoplastic mouse JB6 epidermal cells in response to tumor-promoting phorbol esters, mezerein, or epidermal growth factor, all of which promote neoplastic transformation in JB6 cells, but not in response to the bladder promoter sodium cyclamate, a nonpromoter in JB6 cells. The ganglioside showing elevated synthesis after mezerein or epidermal growth factor exposure is monosialoganglioside 1, whereas disialoganglioside 1b synthesis is elevated after phorbol ester exposure. Primary mouse epidermal cells and putatively initiated epidermal cell lines selected for their resistance to induction of terminal differentiation by high calcium are resistant to promotion of anchorage-independent transformation by 2-week exposure to 12-O-tetradecanoylphorbol-13-acetate. In both cell types, little or no decrease in GT synthesis occurs in response to short-term 12-O-tetradecanoylphorbol-13-acetate exposure, thus extending further our previous observation that this GT response is restricted to promotable cells. A decreased synthesis of GT also occurs consistently in cell lines transformed by 12-O-tetradecanoylphorbol-13-acetate or N-methyl-N-nitro-nitrosoguanidine as compared with their nontransformed counterparts but not in cell lines transformed by a cloned integrated murine sarcoma provirus containing the oncogenic sequence v-mos. Thus, reduced cell surface GT synthesis may be important both in the induction and in the maintenance of the chemically transformed but not viral oncogene mos-transformed phenotype in mouse epidermal cells.
Insights
Tumor promoters decrease trisialoganglioside (GT) synthesis in preneoplastic mouse skin cells, a change linked to neoplastic transformation. This reduction is specific to chemically induced transformations, not those caused by viral oncogenes.
Area of Science:
- Biochemistry
- Cell Biology
- Cancer Research
Background:
- Gangliosides are complex glycosphingolipids found on cell surfaces.
- Trisialoganglioside (GT) levels are altered in various cellular processes, including neoplastic transformation.
- Specific tumor promoters can induce changes in ganglioside synthesis in epidermal cells.
Purpose of the Study:
- To investigate the role of trisialoganglioside (GT) synthesis in neoplastic transformation of mouse JB6 epidermal cells.
- To determine if decreased GT synthesis is a characteristic of chemically induced transformation.
- To compare the effect of different tumor promoters and transforming agents on GT synthesis.
Main Methods:
- Measurement of de novo ganglioside synthesis using [1-14C]-glucosamine incorporation.
- Exposure of preneoplastic mouse JB6 epidermal cells and primary epidermal cells to tumor promoters (phorbol esters, mezerein, epidermal growth factor, sodium cyclamate).
- Analysis of ganglioside profiles in chemically and virally transformed cell lines.
Main Results:
- Tumor promoters (phorbol esters, mezerein, EGF) specifically decreased trisialoganglioside (GT) synthesis in JB6 cells.
- This GT synthesis decrease was observed in promotable JB6 cells but not in resistant primary cells or initiated resistant cell lines.
- Reduced GT synthesis was consistently found in chemically transformed cells but not in cells transformed by v-mos oncogene.
Conclusions:
- A specific decrease in cell surface trisialoganglioside (GT) synthesis is associated with tumor promoter-induced neoplastic transformation in mouse epidermal cells.
- This GT synthesis reduction appears to be a marker for chemically induced transformation, both in its induction and maintenance.
- The observed decrease in GT synthesis is not a feature of transformation mediated by the v-mos oncogene.