Characterization of sarcoma cell lines from v-jun transgenic mice.

Wounding is a prerequisite for tumor formation in v-jun transgenic mice. The progression from wound to dermal sarcoma is a multistep process which, at some stage, results in an increase in transgene mRNA expression in tumor tissue. However, transgene expression in individual sarcoma cells stained for Jun protein cultures is heterogeneous. We cloned several cell lines from wound-related v-jun transgenic tumors to determine whether a relationship existed between the cellular growth properties and structure, expression, or function of the transgene. Cell lines with very high v-jun expression had a high cloning efficiency in soft agar and tumorigenicity in nude mice. However, for cell lines with an intermediate or low level of transgene expression there was no correlation between transgene expression and the transformed phenotype. There was also no correlation between transgene expression and individual cell line morphologies, growth rates, transgene genomic DNA copy number, or mRNA expression of jun-related genes. The tumor cell subclones (1-20.2, 3-24.3) with very low transgene expression, very poor cloning efficiency, and low tumorigenicity also showed reduced activator protein 1 DNA binding activity and had an increased expression of endogenous c-jun when compared to other tumor cell lines. Transfection of a v-jun expression vector into cell lines with poor cloning efficiency and low tumorigenicity enhanced both in vitro cloning and in vivo tumor formation. However, such overexpressed v-jun had no effect on NIH3T3 cells. Our studies show that expression of the v-jun transgene contributes to the transformed phenotype of tumor cell lines but that there are additional factors that determine growth properties in culture and in the animal.