Progression of androgen-sensitive mouse tumor (Shionogi carcinoma 115) to androgen-insensitive tumor after long-term removal of testosterone

Abstract

Shionogi Carcinoma 115 (SC115) is an androgen-sensitive transplantable mouse tumor. To study the mode of progression from androgen-sensitive to -insensitive tumor, cloned SC115 cells were serially cultured without androgen. Shortly after withdrawal of androgen, SC115 cells showed markedly decreased growth, but growth resumed gradually with loss of response to androgen and the cells 60 weeks after androgen removal [A(-)60 cells] grew faster than SC115 cells cultured in the presence of androgen. A(-)60 cells showed malignant phenotype with morphological changes and tumorigenicity in male and female mice. Although mRNA and binding capacity of androgen receptor were maintained, the cells after removal of androgen rapidly lost expression of mouse mammary tumor virus-related gene and the loss was irreversible in A(-)60 cells. The stimulating effect of basic fibroblast growth factor (bFGF) temporarily decreased, then recovered to the initial level after long-term androgen removal. This fluctuation of response to bFGF was accompanied with changes in the number of bFGF receptors and amount of bFGF-like substance(s) secreted. The substance(s) seemed to be an FGF-like growth factor different from known factors. It was concluded that progression of SC115 cells to androgen-insensitive ones under an androgen-deprived condition proceeded with adaptation by means of increases in production of an FGF-like growth factor and in binding capacity to this factor.