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Active cell death in hormone-dependent tissues
M P Tenniswood1, R S Guenette, J Lakins
1Department of Biochemistry, Faculty of Medicine, University of Ottawa, Ontario, Canada.
Abstract:
Active cell death (ACD) in hormone-dependent tissues such as the prostate and mammary gland is readily induced by hormone ablation and by treatment with anti-androgens or anti-estrogens, calcium channel agonists and TGF beta. These agents induce a variety of genes within the hormone-dependent epithelial cells including TRPM-2, transglutaminase, poly(ADP-ribose) polymerase, Hsp27 and several other unidentified genes. Not all epithelial cells in the glands are equally sensitive to the induction of ACD. In the prostate, the secretory epithelial cells that are sensitive to hormone ablation are localized in the distal region of the prostatic ducts, and are in direct contact with the neighboring stroma. In contrast, the epithelial cells in the proximal regions of the ducts are more resistant to hormone ablation, probably because the permissive effects of the stroma are attenuated by the presence of the basal epithelial cells, which are intercalated between the epithelium and stroma. The underlying biology of ACD in prostate and mammary glands, and its relevance to hormone resistance, is discussed in this review.
Insights
Hormone ablation induces active cell death (ACD) in hormone-dependent tissues like the prostate. Differential sensitivity of epithelial cells to ACD is influenced by stromal interactions, impacting hormone resistance.
Area of Science:
- Cell Biology
- Endocrinology
- Oncology
Background:
- Hormone-dependent tissues (prostate, mammary gland) undergo active cell death (ACD) upon hormonal manipulation.
- ACD can be induced by hormone ablation, anti-hormones, calcium channel agonists, and TGF-beta.
- Specific genes like TRPM-2, transglutaminase, PARP, and Hsp27 are upregulated during ACD.
Purpose of the Study:
- To review the underlying biology of active cell death in prostate and mammary glands.
- To discuss the relevance of ACD in the context of hormone resistance.
- To explore the differential sensitivity of epithelial cells to ACD induction.
Main Methods:
- Review of existing literature on active cell death in hormone-dependent tissues.
- Analysis of gene expression changes associated with ACD.
- Examination of cellular localization and stromal interactions in sensitive and resistant cell populations.
Main Results:
- Hormone ablation and specific agents readily induce ACD in hormone-dependent epithelial cells.
- Differential sensitivity to ACD exists among epithelial cells, influenced by location and stromal contact.
- Prostatic secretory cells in distal ducts are sensitive; proximal cells are more resistant due to basal cell-stroma interaction.
Conclusions:
- Stromal interactions play a critical role in modulating epithelial cell sensitivity to ACD.
- Understanding ACD mechanisms is crucial for addressing hormone resistance in prostate and mammary gland cancers.
- Further research into unidentified ACD-related genes may reveal new therapeutic targets.