Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells.

Abstract

Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin. Unexpectedly the human growth hormone-releasing factor (GRF) gene promoter directs expression of SV40 Tag specifically in thymic epithelial (TE) cells. Expression starts in the neonate, in which GRF-Tag+ cells display strict numerical and spatial constraints. Tag supersedes mechanisms that constrain these features and GRF-Tag mice develop thymic hyperplasia. To characterize GRF-Tag+ TE cells and their putative normal counterparts we compared phenotypic and functional effects caused by transgenes encoding mutant large T antigens. This strategy is applicable to any situation in which T antigen is used to alter development. One large Tag mutant (K1 + 5080) does not cause thymic hyperplasia. GRF-Tag (K1 + 5080)+ TE cells display strict temporal and spatial constraints throughout life. TE cells expressing other mutant large T antigens that cause thymic hyperplasia do not obey these rules and reveal that phenotypically distinct GRF-Tag+ TE-cell stages exist in vivo. Analysis of conditional immortal GRF-Tag(tsA58)+ TE cells expressing a temperature-sensitive large Tag shows that large Tag blocks differentiation in these cells. Phenotype and functions in these cells are regulated by cellular differentiation and interleukin 4 (IL-4).

• Authors: J Moll, H Eibel, F Botteri, G Sansig, C Regnier, H van der Putten
• Journal: Oncogene (Oncogene) Vol. 7 Issue 11 Pg. 2175-87 (Nov 1992) ISSN: 0950-9232 [Print] England
• PMID: 1279498 (Publication Type: Journal Article)

Chemical References

• Antigens, Polyomavirus Transforming
• Proto-Oncogene Proteins
• Receptors, Interleukin-4
• Receptors, Mitogen
• Interleukin-4
• Macrophage Colony-Stimulating Factor
• Growth Hormone-Releasing Hormone
• Proto-Oncogene Proteins c-kit

Topics

• Animals
• Antigens, Polyomavirus Transforming (analysis, genetics)
• Cell Differentiation
• Epithelial Cells
• Growth Hormone-Releasing Hormone (genetics)
• Interleukin-4 (pharmacology)
• Macrophage Colony-Stimulating Factor (genetics)
• Mice
• Mice, Inbred C57BL
• Mutation
• Phenotype
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins c-kit
• Receptors, Interleukin-4
• Receptors, Mitogen (genetics)
• Simian virus 40 (immunology)
• Temperature
• Thymus Gland (cytology)