Apoptosis in androgen-independent mouse mammary tumor cells induced by 5-fluorodeoxyuridine but not by androgen withdrawal.

Androgen-dependent tumors eventually progress to independent tumors after androgen withdrawal. Androgen-dependent SC 115 cells could not grow in serum free culture without testosterone. Androgen-independent CS 2 cells, however, could grow whether androgen was present in the media or not. Based upon the temporal sequence of DNA fragmentation, morphological changes and loss of cell viability, androgen withdrawal did not induce the programmed cell death (apoptosis) of CS 2 cells in serum free culture. However, CS 2 cells as well as SC 115 cells retained the ability to undergo apoptosis with 5-fluorodeoxyuridine (FUdR) treatment. Northern blot analysis was used to identify a series of genes and whether the expressions of these per cell changed during apoptotic pathway (i.e. testosterone repressed prostatic message-2; TRPM-2, transforming growth factor-beta 1; TGF-beta 1, glucose regulated 78 kilodalton protein; GRP-78). Although the expression of these genes was increased in SC 115 cells after androgen depletion, none of the genes were induced by androgen withdrawal in CS 2 cells. During the apoptotic process induced by FUdR, mRNA expression of these genes was increased in CS 2 cells as well as in SC 115 cells. These results demonstrate that androgen-independent CS 2 cells do not undergo apoptosis induced by androgen withdrawal, but retain the ability to undergo apoptosis by FUdR. The apoptotic pathway is same whether the cells are androgen-dependent or independent.