Induction of apoptosis in an androgen-independent mouse cell line by transforming growth factor-beta 1.
Androgen-dependent tumors eventually progress to androgen-independent tumors after androgen withdrawal. Androgen-independent CS2 cells could grow in serum-free culture whether androgen is present in the medium or not. In the present study, the mechanism of cell death in CS2 cells was examined after transforming growth factor-beta 1 (TGF-beta 1) treatment. Based upon the temporal sequence of DNA fragmentation, morphologic changes and loss of cell viability, these cells underwent apoptosis with TGF-beta 1 treatment. During the apoptotic process induced by TGF-beta 1, mRNA expression of testosterone repressed prostatic message-2, glucose regulated 78 kDa protein, and calmodulin increased. Flow cytometric analysis showed that TGF-beta 1 treatment resulted in a block in the G0/G1 phase of the cell cycle. These results demonstrate that although androgen withdrawal could not induce apoptosis in androgen-independent CS2 cells, these cells retain the ability to undergo apoptosis induced by TGF-beta 1. This system should be a good model for investigating apoptosis of hormone-independent cancer.
Furuya
Y
Y
Department of Urology, School of Medicine, Chiba University, Japan.
Ohta
S
S
Shimazaki
J
J
D000728:Androgens / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005434:Flow Cytometry; D051379:Mice; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000302:isolation & purification; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000728:Androgens; D012334:RNA, Neoplasm; D016212:Transforming Growth Factor beta; D002118:Calcium; D013936:Thymidine