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Androgen-independent basal cell re-epithelialization, c-erbB-2 mRNA expression and androgen-dependent EGFr mRNA
S Schwartz1, C Caceres, I De Torres
1Unitat de Recerca Biomèdica, Centre d'Investigacions en Bioquímica i Biologia Molecular Vall d'Hebron, Barcelona, Spain. sschwartz@ljcrf.edu
Abstract:
We have analyzed the effects of the 5alpha-reductase inhibitor, finasteride (MK906), on the mRNA expression of the epidermal growth factor receptor and c-erbB-2 genes, in benign prostatic hyperplasia explant cultures treated with testosterone and with testosterone plus finasteride. A decrease of the epithelial cell content and an androgen-independent basal cell re-epithelialization was observed during the first 10 days of culture, suggesting a role of basal cells as stem cells involved in androgen-independent epithelial regeneration. Using a semi-quantitative reverse transcription polymerase chain reaction technique, we observed a significant decrease in expression of the epidermal growth factor receptor in the cultures treated with finasteride whereas no effect of finasteride on c-erbB-2 transcription was detected, although the expression of both genes was increased by dihydrotestosterone.
Insights
Finasteride, a 5alpha-reductase inhibitor, significantly decreased epidermal growth factor receptor mRNA expression in benign prostatic hyperplasia cultures. This suggests finasteride impacts gene expression relevant to prostate tissue regeneration.
Area of Science:
- Urology
- Molecular Biology
- Cell Biology
Background:
- Benign prostatic hyperplasia (BPH) involves complex cellular and molecular changes.
- Epidermal growth factor receptor (EGFR) and c-erbB-2 are implicated in prostate tissue growth and regeneration.
- The role of 5alpha-reductase inhibitors in modulating these gene expressions in BPH is not fully understood.
Purpose of the Study:
- To investigate the effect of finasteride, a 5alpha-reductase inhibitor, on the mRNA expression of EGFR and c-erbB-2.
- To analyze these effects in benign prostatic hyperplasia (BPH) explant cultures under specific hormonal conditions.
Main Methods:
- Utilized benign prostatic hyperplasia (BPH) explant cultures.
- Treated cultures with testosterone and testosterone plus finasteride.
- Employed semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) to measure mRNA expression levels.
Main Results:
- Finasteride treatment led to a significant decrease in epidermal growth factor receptor (EGFR) mRNA expression.
- No significant effect of finasteride on c-erbB-2 gene transcription was observed.
- Dihydrotestosterone (DHT) increased the expression of both EGFR and c-erbB-2 genes.
Conclusions:
- Finasteride significantly downregulates epidermal growth factor receptor (EGFR) mRNA expression in BPH cultures.
- The study highlights a potential mechanism by which finasteride influences prostate tissue, independent of c-erbB-2.
- Basal cells in BPH cultures may act as stem cells, mediating androgen-independent regeneration.