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Antisense TR3 orphan receptor can increase prostate cancer cell viability with etoposide treatment
1George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester, New York 14642, USA.
Abstract:
In androgen-responsive LNCaP human prostatic cancer cells, human TR3 orphan receptor, a member of the steroid receptor superfamily, can be rapidly induced by androgen. In contrast, ablation of androgen by castration can induce the expression of the TR3 orphan receptor gene in rat ventral prostate that has undergone apoptosis. This phenomenon prompted us to further analyze the potential role of human TR3 orphan receptor in prostate cancer cells in which apoptosis had been induced. Northern blot analysis shows that human TR3 orphan receptor expression can be induced rapidly after treatment of LNCaP and PC-3 prostate cancer cells with calcium ionophore or etoposide. Our data further demonstrate that a much higher concentration of etoposide was needed to kill the same number of cells in LNCaP and PC-3 cells transfected stably with antisense TR3 orphan receptor compared with that in control vector transfectants. Together, our data suggest that the human TR3 orphan receptor may play an important role in modulating drug-induced prostate apoptosis.
Insights
The human TR3 orphan receptor is rapidly induced in prostate cancer cells during apoptosis. This receptor appears to play a role in modulating drug-induced prostate cancer cell death.
Area of Science:
- Molecular Endocrinology
- Cancer Biology
- Prostate Cancer Research
Background:
- The human TR3 orphan receptor, a steroid receptor superfamily member, is androgen-inducible in LNCaP cells.
- TR3 expression is also induced in rat prostate following androgen ablation and apoptosis.
Purpose of the Study:
- To investigate the role of the human TR3 orphan receptor in drug-induced apoptosis of prostate cancer cells.
- To analyze the modulation of apoptosis by TR3 in prostate cancer models.
Main Methods:
- Northern blot analysis to assess TR3 gene expression.
- Transfection of prostate cancer cells (LNCaP and PC-3) with antisense TR3 or control vectors.
- Treatment with calcium ionophore and etoposide to induce apoptosis.
Main Results:
- Human TR3 orphan receptor expression was rapidly induced by calcium ionophore or etoposide in LNCaP and PC-3 cells.
- Cells stably transfected with antisense TR3 required higher etoposide concentrations for cell death compared to controls.
- This suggests TR3 plays a role in resistance to etoposide-induced apoptosis.
Conclusions:
- The human TR3 orphan receptor is involved in the apoptotic process of prostate cancer cells.
- TR3 may act as a modulator of drug-induced apoptosis in prostate cancer, potentially influencing treatment efficacy.