Induction of Programmed Death/Apoptosis in Androgen‐dependent Mouse Mammary Tumor Cell Line (Shionogi Carcinoma 115) by Androgen Withdrawal

Abstract

Shionogi Carcinoma 115 (SC 115) cells are a cloned cell line derived from androgen‐dependent mouse mammary tumor. They can grow in serum‐free culture if a physiological level of androgen is present in the medium, but can not proliferate in culture without testosterone. In the present study, the mechanism of cell death in SC 115 cells after androgen withdrawal was examined . Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, androgen withdrawal induces programmed cell death (apoptosis) of SC 115 cells in serum‐free culture. Northern blot analysis was used to identify a series of genes whose expression per cell is enhanced during the recruitment of cells from a nonproliferative (i.e. G0) state into G1 (i.e., cyclins Dl and C), from G1 into the S phase of the cell cycle (i.e., cdk2), and during the programmed cell death pathway (i.e. testosterone repressed prostatic message‐2 (TRPM‐2), transforming growth factor‐β1 (TGF‐β1) and glucose regulated 78 kilodalton protein (GRP‐78)). Expression of TRPM‐2, TGF‐β1, GRP‐78, and calmodulin genes increases, but that of cyclins C and Dl, and cdk2 genes decreases during programmed cell death of SC 115 cells. These results demonstrate that androgen‐dependent SC 115 cells undergo programmed cell death induced by androgen withdrawal, and that this death does not require proliferation or progression into Gi of the proliferative cell cycle. SC 115 cells should be a good model for investigating programmed death of hormone‐dependent cancer.