Transformation of a rat liver cell line: neoplastic phenotype and regulation of gamma glutamyl transpeptidase in tumour tissue.

A continuously dividing but non-transformed rat cell line was transformed by ras oncogenes and by aflatoxin. Transformed lines grew as solid tumours in nude mice with a short latency period. Different phenotypes were obtained from the transformed clones, and covered a wide spectrum of tumour types. While the commonest tumour type obtained was undifferentiated with unorganized spindle shaped and rounded cells, tumours with well formed trabeculae and adenomatous differentiation were also obtained. Gamma glutamyl transpeptidase (GGT), which showed an increase in transformed cells in tissue culture showed a variable expression in nude mouse tumours. While GGT positive cells were seen in all types of tumours they followed no consistent pattern and GGT negative areas were seen with a high frequency. However, in tumours showing adenomatous differentiation it was confined to the membrane on the luminal surface of the glandular structures. The different types of tumours resulting from the transformation of a single cell line provide a model of in vivo tumour development, supporting the possibility of a single stem cell origin of different types of liver neoplasms. This system also demonstrates the complexity of the regulation of GGT in tumour tissue. The influence of GGT on tumorigenesis has also been studied.