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Induction of apoptosis in an androgen-independent mouse cell line by transforming growth factor-beta 1
Y Furuya1, S Ohta, J Shimazaki
1Department of Urology, School of Medicine, Chiba University, Japan.
Abstract:
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.
Insights
Androgen-independent cancer cells undergo apoptosis when treated with transforming growth factor-beta 1 (TGF-beta 1). This response involves cell cycle arrest and increased specific gene expression, offering a model for hormone-independent cancer research.
Area of Science:
- Oncology
- Cell Biology
- Molecular Biology
Background:
- Androgen-dependent tumors can progress to androgen-independent forms.
- Androgen-independent CS2 cells proliferate irrespective of androgen presence.
- Understanding cell death mechanisms in hormone-independent cancers is crucial.
Purpose of the Study:
- To investigate the mechanism of cell death in androgen-independent CS2 cells following transforming growth factor-beta 1 (TGF-beta 1) treatment.
- To determine if CS2 cells retain the capacity for apoptosis induction.
- To establish a model for studying apoptosis in hormone-independent cancers.
Main Methods:
- Treatment of CS2 cells with TGF-beta 1.
- Assessment of DNA fragmentation, morphologic changes, and cell viability.
- Analysis of mRNA expression for specific genes (testosterone repressed prostatic message-2, glucose regulated 78 kDa protein, calmodulin).
- Flow cytometric analysis of cell cycle progression.
Main Results:
- TGF-beta 1 treatment induced apoptosis in CS2 cells, evidenced by DNA fragmentation, morphological changes, and reduced viability.
- Apoptosis induction by TGF-beta 1 was associated with increased mRNA expression of testosterone repressed prostatic message-2, glucose regulated 78 kDa protein, and calmodulin.
- TGF-beta 1 treatment caused a cell cycle block at the G0/G1 phase.
- Androgen withdrawal alone did not induce apoptosis in these cells.
Conclusions:
- Androgen-independent CS2 cells, while resistant to androgen withdrawal-induced apoptosis, can undergo apoptosis mediated by TGF-beta 1.
- TGF-beta 1 serves as an effective inducer of apoptosis in this model system.
- The CS2 cell system provides a valuable platform for investigating apoptosis in hormone-independent cancers.