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Oncogene transgenic mice: an useful model to study in vivo the relationships between gangliosides and oncogenes
I Colombo1, E Monteggia, S Moretti
1Institute of General Physiology and Biological Chemistry, University of Milan, Italy.
Abstract:
Several studies have demonstrated that transfer of oncogenes in cultured cells reproducibly induces transmissible alterations in their ganglioside profile; the transfection of the same oncogene into different cell lines and the different localization of the oncogene product result in a different ganglioside expression. In the present study the modifications of the ganglioside pattern in mammary carcinomas induced in transgenic mice by the activated form of the rat neu oncogene have been investigated. Whereas control mammary tissues contain quite exclusively GM3, all neoplastic samples show a substantial decrease of this ganglioside, an accumulation in variable amount of GM3-derived species (GM1, GD3, GD1a, GD1b, GT and GQ) and the appearance of new, not yet identified, sialic acid containing molecules. Interestingly, three out of 10 tumors analyzed, even if histologically comparable to the others but with a larger dimension, show a significative difference as regard to the GM1, GD3 and GD1a content. Our data suggest that an activated oncogene may induce also in vivo a specific and transmissible alteration in the ganglioside pattern, but this distribution could be susceptible to further modifications during the tumor progression.
Insights
Activated oncogenes alter ganglioside profiles in mouse mammary tumors, decreasing GM3 and increasing complex forms. Tumor progression may further modify these specific ganglioside patterns.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Oncogene transfer in cell cultures alters ganglioside profiles.
- Ganglioside expression varies with oncogene and cell type.
Purpose of the Study:
- Investigate ganglioside pattern modifications in mammary carcinomas induced by an activated rat neu oncogene in transgenic mice.
- Determine if oncogene activation causes specific in vivo ganglioside alterations.
Main Methods:
- Analysis of ganglioside expression in neoplastic mammary tissues from transgenic mice harboring an activated rat neu oncogene.
- Comparison of ganglioside profiles between tumor samples and control mammary tissues.
Main Results:
- Control tissues predominantly expressed GM3.
- Neoplastic samples showed decreased GM3, accumulation of GM3-derived species (GM1, GD3, GD1a, GD1b, GT, GQ), and novel sialic acid-containing molecules.
- Larger tumors exhibited distinct GM1, GD3, and GD1a content compared to smaller, histologically similar tumors.
Conclusions:
- Activated oncogenes induce specific, transmissible ganglioside pattern alterations in vivo.
- Ganglioside distribution in tumors can change during tumor progression.