Characteristics of androgen-independent growth of androgen-responsive Shionogi carcinoma 115 cells.

BACKGROUND

The effects of castration on the biological features of an androgen-responsive carcinoma were examined in order to clarify the mechanism responsible for the relapse of an androgen-responsive carcinoma after androgen ablation therapy.

METHODS

A well-characterized androgen-responsive mammary carcinoma, Shionogi carcinoma 115 (SC115), was used for these experiments. Male mice were examined for the effects of castration on the growth rate of the tumor, the number of androgen receptor-positive cells, and the karyotype of the SC115 tumors. Castration was performed 1 week prior to tumor transplantation, or 2 or 3 weeks after tumor transplantation.

RESULTS

SC115 tumors did not develop when transplanted into castrated male mice. When castration was performed 2 weeks after transplantation, the tumor showed androgen-independent growth with temporary regression of growth rate. However, when castration was performed more than 3 weeks after transplantation, the tumor showed androgen-independent growth not associated with any temporal regression of growth rate. There were no significant differences in histological features or the number of androgen receptor-positive cells between SC115 tumors in untreated or castrated mice. To test whether SC115 tumors growing under androgen-deprived conditions became fully androgen-independent, SC115 tumors were transplanted in both male and female mice. A transplanted tumor piece grew progressively only in male mice. This indicates that the SC115 tumor maintains its androgen response in the next generation, even though growth of the tumor resumed after temporary suppression due to castration. Chromosomal analyses revealed no apparent cytogenetic changes in the SC115 tumors that resumed growth under androgen-deprived conditions.

CONCLUSION

These results suggest that no gross changes in the number of androgen receptor-positive cells or karyotype are necessary for androgen-independent growth in this system once the size of tumor increased.